ОБЗОРЫ

Лимфомы у ВИЧ-инфицированных больных: обзор литературы

ОБЗОРЫ

А.В. Пивник1, М.В. Туманова1, Н.В. Серегин2, Ю.Г. Пархоменко3,4, О.А. Тишкевич4, А.М. Ковригина5, Е.Б. Ликунов6

1 Московский клинический научно-практический центр им. Д.Д. Плетнева Департамента здравоохранения, Москва, Российская Федерация

2 Московский городской онкологический диспансер № 3, Москва, Российская Федерация

3 ФГБУ «Научно-исследовательский институт морфологии человека» РАМН, Москва, Российская Федерация

4 КИБ № 2 Департамента здравоохранения, Москва, Российская Федерация

5 ФГБУ «Гематологический научный центр» МЗ РФ, Москва, Российская Федерация

6 Американский медицинский центр, Москва, Российская Федерация

Для цитирования: Пивник А.В., Туманова М.В., Серегин Н.В., Пархоменко Ю.Г., Тишкевич О.А., Ковригина А.М., Ликунов Е.Б. Лимфомы у ВИЧ-инфицированных больных: обзор литературы. Клин. онкогематол. 2014; 7(3): 264–77

РЕФЕРАТ

В обзоре изложены материалы статей зарубежных и отечественных авторов по частоте, патогенезу, диагностике и лечению злокачественных лимфопролиферативных заболеваний у ВИЧ-инфицированных пациентов. Подчеркивается главенствующая роль снижения числа лимфоцитов CD4+ в развитии вторичных заболеваний при ВИЧ-инфекции. Приводятся данные отечественных авторов о структуре причин смерти у ВИЧ-инфицированных пациентов, где из 6 основных причин смерти на 5-м месте лимфомы. Лимфома Ходжкина у ВИЧ-инфицированных пациентов в обзоре специально не обсуждается, поскольку ее патогенез отличается от такового агрессивных лимфом и требует отдельного освещения.

Ключевые слова: лимфомы у ВИЧ-инфицированных пациентов, ВИЧ, СПИД, вторичные заболевания, причины смерти, патогенез, диагностика, лечение.

Принято в печать: 15 мая 2014 г.

Читать статью в PDFpdficon

ЛИТЕРАТУРА

  1. Ship J.A., Wolff A., Selik R.M. Epidemiology of acquired immune deficiency syndrome in persons aged 50 years or older. J. Acquir. Immune Defic. Syndr. 1991; 4(1): 84–8.
  2. Lyles R.H., Munoz A., Yamashita T.E. et al. Natural history of HIV type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. J. Infect. Dis. 2000; 181: 872–80.
  3. Бобкова М.Р. Иммунитет и ВИЧ-инфекция (популярные лекции). М.: Олимпия Пресс, 2006. 240 с. [Bobkova M.R. Immunitet i VICh-infektsiya (populyarnye lektsii). (Immunity and HIV infection (popular lectures)). Moscow: Olimpiya Press Publ., 2006. 240 p.].
  4. Mellors J.W., Munoz A.M., Giorgi J.V. et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann. Intern. Med. 1997; 126: 946–54.
  5. UNAIDS Technical Update (UNAIDS Best Practice Collection: Technical Update). UNAIDS (1997b): HIV testing methods. Geneva: UNAIDS, November 1997.
  6. Покровский В.В., Ермак Т.Н., Беляева В.В. ВИЧ инфекция. Клиника, диагностика, лечение. М.: ГЭОТАР-Медиа, 2003: 356–60. [Pokrovskii V.V., Ermak T.N., Belyaeva V.V. VICh infektsiya. Klinika, diagnostika, lechenie. (HIV infection. Clinical picture, diagnosis, treatment). Moscow: GEOTAR-Media Publ., 2003. pp. 356–60].
  7. ВИЧ-инфекция и СПИД: национальное руководство. Под. ред. В.В. Пок ровского. М.: ГЭОТАР-Медиа, 2013. 608 с.  [Pokrovskii V.V., ed. VICh-infektsiya i SPID: natsional’noe rukovodstvo. (HIV and AIDS: national guidelines). Moscow: GEOTAR-Media Publ., 2013. 608 p.].
  8. Покровский В.И., Покровский В.В., Потекаев С.Н. и др. Первый случай СПИД у гражданина СССР. Тер. арх. 1988; 7: 10–14. [Pokrovskii V.I., Pokrovskii V.V., Potekaev S.N. et al. The first case of AIDS in a USSR resident. Ter. arkh. 1988; 7: 10–4. (In Russ.)].
  9. Тишкевич О.А., Шахгильдян В.И., Пархоменко Ю.Г. Структура ле- тальных исходов и патологическая анатомия у больных ВИЧ-инфекцией в Москве. Эпидемиол. и инфек. бол. 2004; 4: 42–6. [Tishkevich O.A., Shakhgil’dyan V.I., Parkhomenko Yu.G. The Structure of lethal outcomes and morbid anatomy in HIV infected patients in Moscow. Epidemiol. i infek. bol. 2004; 4: 42–6. (In Russ.)].
  10. Гармаева Т.Ц. Вирусные гепатиты В и С у больных заболеваниями системы крови: Автореф. дис. … д-ра мед. наук. М., 2012. [Garmaeva T.Ts. Virusnye gepatity B i C u bol’nykh zabolevaniyami sistemy krovi: Avtoref. dis. … d-ra med. nauk. (Viral hepatitis B and C in patients with blood diseases: Author’s abstract of doctor’s thesis). Moscow, 2012.].
  11. Gonzalez R., Jacobus J., Martin M. Investigating Neurocognitive Features of Hepatitis C Virus Infection in Drug Users: Potential Challenges and Lessons Learned from the HIV Literature. CID 2005; 41: S45–49.
  12. Hilsabeck R.C., Castellon S.A., Hinkin Ch.H. Neuropsychological Aspects of Coinfection with HIV and Hepatitis C Virus. CID 2005; 41: S38–44.
  13. Desai J., Mitnick R.J., Henry D.H., Llena J., Sparano J.A. Patterns of central nervous system recurrence in patients with systemic human immunodeficiency virus-associated non-Hodgkin lymphoma. Cancer 1999; 86: 1840–7.
  14. Леви Дж.Э. ВИЧ и патогенез СПИДа: Пер. с англ., 3-е изд. М.: На- учный мир, 2010: 16. [Levy Jay A. HIV and the Pathogenesis of AIDS. 3rd edition. ASM Press, 2007, 643 p. (Russ. Ed. Levy J.A. VICh i patogenez SPIDa. Moscow: Nauchnyi Mir Publ., 2010. рр. 16.)].
  15. Allers K., Hutter G., Hofmann J. et al. Evidence for the cure of HIV infection 32 stem cell transplantation. Blood 2011; 117(10): 2791–9.D32/Dby CCR5
  16. Hosseini I., MacGabhann F., Thomas P.G. (eds.) APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study. PLoS One 2013; 8(5): e63984.
  17. Kenneth L.M., Johnson M., D’Aquila R.T. APOBEC3G Complexes Decrease Human Immunodeficiency Virus Type 1 Production. J. Virol. 2011; 85(18): 9314–26.
  18. Collins K.L., Chen B.K., Walker B.D., Baltimore D. HIV-1 protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 1998; 391: 397–401.
  19. Hammer S.M. Treatment for adult HIV infection: JAVA 2006; 296(7): 827–43.
  20. Hoffmann C., Chow K.U., Wolf E. et al. Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virusassociated Hodgkin’s disease. Br. J. Haematol. 2004; 125: 455.
  21. Хоффман К., Кампс Б. Лечение ВИЧ-инфекции. Flying Publisher, 2005. 581 c. [Hoffmann C., Kamps B. HIV Therapy. Flying Publisher, 2005. 581 p. (Russ. Ed. Hoffmann C., Kamps B. Lechenie VICh-infektsii. Flying Publisher, 2005. 581 p.)].
  22. Бартлетт Дж. и др. Клинические аспекты ВИЧ-инфекции: Пер. с англ. М., 2013. 540 с. [Bartlett J. et al. Klinicheskie aspekty VICh-infekcii (Clinical aspects of HIV infection). Moscow, 2013. 540 p.].
  23. Ioachim H.L. Lymphadenopathies of HIV infection and AIDS. In: Benign and malignant lymphadenopathies. Ed. by G.A. Pangalis, A. Polliack. Harwood academic publisher, 1993: 159–70.
  24. Малый В.П. ВИЧ/СПИД (Новейший медицинский справочник). М.: Эксмо, 2009. 672 с. [Malyi V.P. VICh/SPID (Noveishii meditsinskii spravochnik) (HIV/AIDS (Up-todate manual)). Moscow: Eksmo Publ., 2009. 672 p.].
  25. Пивник А.В., Лукашев А.М., Туманова М.В. и др. Диагностика и ле- чение больных СПИД-ассоциированными лимфомами. Вестн. Моск. онкол. общества. 2008; 12: 553. [Pivnik A.V., Lukashev A.M., Tumanova M.V. et al. Diagnosis and treatment of patients with AIDS-associated lymphomas. Vestn. Mosk. onkol. obshchestva. 2008; 12: 553. (In Russ.)].
  26. Schuerman D.A. Clinical concerns: AIDS in the elderly. J. Gerontol. Nurs. 1994; 20(7): 11–7.
  27. Пархоменко Ю.Г., Тишкевич О.А., Шахгильдян В.И. Анализ аутопсий при ВИЧ-инфекции. Арх. пат. 2003; 3: 24–9. [Parkhomenko Yu.G., Tishkevich O.A., Shakhgil’dyan V.I. Analysis of autopsies in HIV infection. Arkh. pat. 2003; 3: 24–9. (In Russ.)].
  28. Mack K.A., Ory M.G. AIDS and older Americans at the end of the twentieth century. J. Acquir. Immune Defic. Syndr. 2003; 33(Suppl. 2): S68–75.
  29. Diamond C., Taylor T.H., Im T., Miradi M., Anton-Culver H. Improved survival and chemotherapy response among patients with AIDS-related Hodgkin’s lymphoma receiving highly active antiretroviral therapy. Hematol. Oncol. 2006; 10: 10.
  30. Powles T., Imami N., Nelson M., Gazzard B.G., Bower M. Effects of combination chemotherapy and HAART on immune parameters in HIV-1 associated lymphoma. AIDS 2002; 16: 531–6.
  31. Пивник А.В., Коровушкин В.Г., Пархоменко Ю.Г. и др. Дифференци- альная диагностика лимфаденопатий при ВИЧ/СПИД. Тер. арх. 2006; 4: 28–32. [Pivnik A.V., Korovushkin V.G., Parkhomenko Yu.G. et al. Differential diagnosis of lymphoadenopathies in HIV/AIDS. Ter. arkh. 2006; 4: 28–32. (In Russ.)].
  32. Пивник А.В., Коровушкин В.Г., Туаева А.О. и др. Тромбоцитопения при ВИЧ-инфекции. Тер. арх. 2008; 80(7): 75–80. [Pivnik A.V., Korovushkin V.G., Tuaeva A.O. et al. Thrombocytopenia in HIV infection. Ter. arkh. 2008; 80(7): 75–80. (In Russ.)].
  33. Малеев В.В., Полякова А.М., Кравченко А.В. Патогенетические механизмы нарушений системы гемостаза у больных ВИЧ-инфекцией. Эпидемиол. и инфек. бол. 2000; 3: 45–9. [Maleev V.V., Polyakova A.M., Kravchenko A.V. Pathogenetic mechanisms of hemostatic disorders in HIV infected patients. Epidemiol. i infek. bol. 2000; 3: 45–9. (In Russ.)].
  34. Stebbing J., Gazzard B., Mandalia S. et al. Antiretroviral treatment regimens and immune parameters in the prevention of systemic AIDS-related non-Hodgkin’s lymphoma. J. Clin. Oncol. 2004; 22(11): 2177–83.
  35. Young N.S., Gerson S.L., High K.A. Clinical Hematology. Philadelphia: Mosby Elsevier, 2006: 505–79.
  36. Февралева И.С., Глинщикова О.А., Макарик Т.В., Судариков А.Б. Мультиплексная диагностика вирусов гепатитов В, С и парвовируса В19 у больных, получающих множественные гемотрансфузии. Гематол. и транс- фузиол. 2008; 53(4): 54–6. [Fevraleva I.S., Glinshchikova O.A., Makarik T.V., Sudarikov A.B. Multiplex diagnosis of hepatitis B and C viruses and parvovirus B19 in patients receiving multiple hemotransfusions. Gematol. i transfuziol. 2008; 53(4): 54–6. (In Russ.)].
  37. Судариков А.Б. Молекулярная диагностика вирусов гепатита С, В, G и парвовируса B19 у гематологических больных: Автореф. дис. д-ра … биол. наук. М., 2012. [Sudarikov A.B. Molekulyarnaya diagnostika virusov gepatita S, V, G i parvovirusa  B19 u gematologicheskikh bol’nykh: Avtoref. dis. … d-ra biol. nauk. (Molecular diagnosis of hepatitis C, B, G viruses and parvovirus B19 in hematological patients). Moscow, 2012.].
  38. Wu H., Kuritzkes D.R., Clemon D.R. et al. Characterization of viral dynamics in HIV type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points. J. Infect. Dis. 1999; 179: 799–807.
  39. Ganellos G.P., Lister T.A., Sklar J.L. The Lymphomas. Philadelphia: W.B. Saunders, 1998: 399–413.
  40. Armitage J.O., Cavalli F., Longo D. Annual of Lymphoid Malignancies. Taylor & Francis, 2000: 112–9.
  41. Navarro W.H., Kaplan L.D. AIDS-related lymphoproliferative disease. Blood 2006; 107(1): 13–20. 42. Little R.F. AIDS-related non-Hodgkin’s lymphoma: etiology, epidemiology, and impact of highly active antiretroviral therapy. Leuk. Lymphoma 2003; 44(3): 63–8.
  42. Gerard L., Galicier L., Maillard A. et al. Systemic non-Hodgkin lymphoma in HIV-infected patients with effective suppression of HIV replication: persistent occurrence but improved survival. J. Acquir. Immune Defic. Syndr. 2002; 30: 478–84.
  43. Levine A.M., Seneviratne L., Espina B.M. et al. Evolving characteristics of AIDS-related lymphoma. Blood 2000; 96: 4084–90.
  44. Matthews G.V., Bower M., Mandalia S. et al. Changes in AIDS-related lymphoma since the introduction of HAART. Blood 2000; 96: 2730–4.
  45. Besson C., Goubar A., Gabarre J. et al. Changes in AIDS-related lymphoma since the era of HAART. Blood 2001; 98: 2339–44.
  46. Levine A.M. AIDS-related lymphoma. Semin. Oncol. Nurs. 2006; 22(2): 80–9.
  47. Aboulafia D.M., Pantanowitz L., Dezube B.J. AIDS-Related Non-Hodgkin Lymphoma: Still a Problem in the Era of HAART. AIDS 2004; 14(11): 605–17.
  48. Kadan-Lottick N.S., Skluzacek M.C., Gurney J.G. Decreasing incidence rates of primary central nervous system lymphoma. Cancer 2002; 95: 193–202.
  49. Franceschi S., Dal Maso L., La Vecchia C. Advances in the epidemiology of HIV-associated non-Hodgkin’s lymphoma and other lymphoid neoplasms. Intern. J. Cancer 1999; 83: 481–5.
  50. Cinque P., Brytting M., Vago L. et al. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1993; 342: 398–401.
  51. Oriol A., Ribera J.M., Esteve J. et al. Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMALAL3/97 study. Haematologica 2003; 88(4): 445–53.
  52. Mounier N., Spina M., Gabarre J. et al. AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk adapted intensive chemotherapy. Blood 2006; 107(10): 3832–40.
  53. Lim S.T., Karim R., Tulpule A., Nathwani B.N., Levine A.M. Prognostic Factors in HIV-Related Diffuse Large-Cell Lymphoma: Before Versus After Highly Active Antiretroviral Therapy. J. Clin. Oncol. 2005; 23(33): 8477–82.
  54. Carbone A., Cesarman E., Spina M. HIV-associated lymphomas and gamma-herpesviruses. Blood 2009; 113(6): 1213–24.
  55. Simonelli C., Spina M., Cinelli R. et al. Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J. Clin. Oncol. 2003; 21: 3948–54.
  56. Menendez J.A., Lilien D.L., Nanda А. et al. AIDS-Related Lymphoma. Abstr. Hematol. Oncol. 2005; 8(1): 20–30, 68–70.
  57. Delecluse H.J., Anagnostopoulos I., Dallenbach F. et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. Blood 1997; 89: 1413–20.
  58. Gisselbrecht C., Mounier N. Treatment of relapsed and refractory Hodgkin’s Lymphoma. In: Education program of the 10th congress of the European Hematology Association, 2005: 182–5.
  59. Gisselbrecht C., Mounier N. Treatment of poor prognosis non-Hodgkin’s lymphoma. In: Education program of the 10th congress of the European hematology association, 2005: 160–5.
  60. Bower M., Gazzard B., Mandalia S., Newsom-Davis T. et al. A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy. Ann. Intern. Med. 2005; 143: 265–73.
  61. Feigal E.G., Levine A.M., Biggar R.J. AIDS-related Cancers and Their Treatment. Marcel Dekker Inc., 2000: 97–124.
  62. Little R.F., Gutierrez M., Jaffe E.S. et al. HIV-Associated non-Hodgkin lymphoma: incidence, presentation, and prognosis. JAMA 2001; 285: 1880–5.
  63. Pauza C.D., Pyzalski R., Perlman S.B. et al. Positron emission tomography images of AIDS pathogenesis. Conf. Adv. AIDS Vaccine, 1997.
  64. Литвинов В.И., Макарова М.В., Краснова М.А. Нетуберкулезные микобактерии и микобактериозы. Эпидемиол. и инфек. бол. 2011; 6: 4–10. [Litvinov V.I., Makarova M.V., Krasnova M.A. Nontuberculous mycobacteria and mycobacteriosis. Epidemiol. i infek. bol. 2011; 6: 4–10. (In Russ.)].
  65. Литвинов В.И., Макарова М.В., Краснова М.А. Нетуберкулезные микобактерии. М.: МНПЦБТ, 2008. 256 с.  [Litvinov V.I., Makarova M.V., Krasnova M.A. Netuberkuleznye mikobakterii (Nontuberculous mycobacteria). Moscow: MNPTsBT Publ., 2008. 256 р.].
  66. Clarke C.A., Glaser S.L. Epidemiologic trends in HIV-associated lymphomas. Curr. Opin. Oncol. 2001; 13: 354–9.
  67. Clarke C.A., Glaser S.L. Epidemiologic trends in HIV-associated lymphomas. Curr. Opin. Oncol. 2003; 15: 267–90.
  68. Патологическая анатомия: национальное руководство. Под ред. М.А. Пальцева, Л.В. Кактурского, О.В. Зайратьянца. М.: ГЭОТАР-Медиа, 2011. 1264 с. [Pal’tsev M.A., Kakturskii L.V., Zairat’yants O.V., eds. Patologicheskaya anatomiya: natsional’noe rukovodstvo. (Morbid anatomy: national guidelines). Moscow: GEOTAR-Media Publ., 2011. 1264 p.].
  69. Stebbing J., Marvin V., Bower M. et al. The evidence-based treatment of AIDS-related non-Hodgkins lymphoma. Cancer Treat. Rev. 2004; 30: 249–53.
  70. Hartmann P., Rehwald U., Salzberger B. et al. BEACOPP therapeutic regimen for patients with Hodgkin’s disease and HIV infection. Ann. Oncol. 2003; 14: 1562–9.
  71. Antinori A., Cingolani A., Alba L. et al. Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy. AIDS 2001; 15: 1483–91.
  72. Chadburn A., Hyjek E., Mathew S. et al. KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. Am. J. Surg. Pathol. 2004; 28(11): 1401–16.
  73. Пивник А.В. Применение ритуксимаба у больных с ВИЧ-инфекцией. Клин. онкогематол. 2013; 6(1): 84–90.  [Pivnik A.V. The use of rituximab in patients with HIV infection. Klin. onkogematol. 2013; 6(1): 84–90. (In Russ.)].
  74. Lim S.T., Karim R., Nathwani B.N. et al. AIDS-related Burkitt’s lymphoma versus diffuse large cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy. J. Clin. Oncol. 2005; 23: 4430–8.
  75. Boue F., Gabarre J., Gisselbrecht C. et al. CHOP chemotherapy plus Rituximab in HIV patients with high grade lymphoma – results of an ANRS Trial. Blood 2002; 22: 470a (abstract 1824).
  76. Dunleavy K., Wilson W.H. How I treat HIV-associated lymphoma. Blood 2012; 119(14): 3245–55.
  77. Krishnan A., Molina A., Zaia J. et al. Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 2005; 105(2): 874–8.
  78. Sparano J.A., Wiernik P.H., Strack M. et al. Infusional cyclophosphamide, doxorubicin, and etoposide in human immunodeficiency virus- and human T-cell leukemia virus type I-related non-Hodgkin’s lymphoma: a highly active regimen. Blood 1993; 81: 2810–5.
  79. Cortes J., Thomas D., Rios A. et al. Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Cancer 2002; 94: 1492–9.
  80. Molina A., Zaia J., Krishnan A. Treatment of human immunodeficiency virus-related lymphoma with haematopoietic stem cell transplantation. Blood Rev. 2003; 17: 249–58.
  81. Navarro J.T., Ribera J.M., Oriol A. et al. Influence of HAART on response to treatment and survival in patients with AIDS-related non-Hodgkin’s lymphoma treated with cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone. Br. J. Haematol. 2001; 112: 909–15.
  82. Барях Е.А., Кременецкая А.М., Кравченко С.К. и др. Новый короткий высокоинтенсивный протокол терапии лимфомы Беркитта у взрослых ЛБ- М-04: промежуточные результаты. Гематол. и трансфузиол. 2006; 51(6): 45–9. [Baryakh E.A., Kremenetskaya A.M., Kravchenko S.K. et al. New abridged highly intensive protocol LB-M-04 for treatment of Burkitt’s lymphoma in adults: interim results. Gematol. i transfuziol. 2006; 51(6): 45–9. (In Russ.)].
  83. Барях Е.А., Звонков Е.Е., Кременецкая А.М. и др. Лечение Беркитто- подобной лимфомы у взрослых. Тер. арх. 2005; 7: 53–8. [Baryakh E.A., Zvonkov E.E., Kremenetskaya A.M. et al. Treatment of Burkittlike lymphoma in adults. Ter. arkh. 2005; 7: 53–8. (In Russ.)].
  84. Пивник А.В., Пархоменко Ю.Г., Криволапов Ю.А. и др. Соматические проблемы ВИЧ-медицины: СПИД-ассоциированные лимфомы. Онкогема- тология 2007; 3: 27–37. [Pivnik A.V., Parkhomenko Yu.G., Krivolapov Yu.A. et al. Somatic problems of HIV medicine: AIDS-associated lymphomas. Onkogematologiya 2007; 3: 27–37. (In Russ.)].
  85. Kaplan L.D., Lee J.Y., Ambinder R.F. еt al. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin’s lymphoma: AIDS-Malignancies Consortium Trial 010. Blood 2005; 106: 1538–43.
  86. Kaplan L.D., Scadden D.T. No benefit from Rituximab in a randomized phase III trial of CHOP with or without rituximiab for patients with HIV-associated non-Hodgkins lymphoma: AIDS-Malignancies Consortium study 010. Proc. Am. Soc. Clin. Oncol. 2003; 22: 564 (abstract 2268).
  87. Krishnan A., Molina A., Zaia J. et al. Autologous stem cell transplantation for HIV-associated lymphoma. Blood 2001; 98: 3857–9.

Передача сигнала через B-клеточный рецептор: механизмы и ингибиторы

ОБЗОРЫ , ,

E.A. Никитин

ФГБУ «Гематологический научный центр» МЗ РФ, Москва, Российская Федерация

Для цитирования: Никитин E.A. Передача сигнала через B-клеточный рецептор: механизмы и ингибиторы. Клин. онкогематол. 2014; 7(3): 251–63.

РЕФЕРАТ

Сигнальный путь В-клеточного рецептора (BCR) имеет ключевое значение в жизнеспособности и дифференцировке нормальных В-лимфоцитов. Клетки лимфоидных опухолей используют различные аспекты этого сигнального пути для обеспечения пролиферации и роста. Они проявляются в разных формах: в форме особой антигенной специфичности BCR, в форме активирующих или, наоборот, ингибирующих мутаций генов, кодирующих белки пути BCR. Целый ряд малых молекул подавляют различные компоненты пути BCR.

В обзоре рассматривается передача сигнала через BCR в норме и патологии, а также ингибиторы тирозинкиназ, которые активно используются в клинических исследованиях, и, возможно, уже скоро изменят тактику ведения больных с лимфоидными опухолями.

Ключевые слова: В-клеточные лимфомы, В-клеточный рецептор, ингибиторы киназ.

Принято в печать: 8 мая 2014 г

Читать статью в PDFpdficon

ЛИТЕРАТУРА

  1. Dameshek W., Schwartz R.S. Leukemia and auto-immunization-some possible relationships. Blood 1959; 14: 1151–8.
  2. Goodlad J.R. et al. Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the Highlands of Scotland. Am. J. Surg. Pathol. 2000; 24(9): 1279–85.
  3. Vasudevan B., Chatterjee M. Lyme borreliosis and skin. Indian J. Dermatol. 2013; 58(3): 167–74.
  4. Schollkopf C., Melbye M., Munksgaard L. et al. Borrelia infection and risk of non-Hodgkin lymphoma. Blood 2008; 111(12): 5524–9.
  5. Garbe C., Stein H., Dienemann D., Orfanos C.E. Borrelia burgdorferiassociated cutaneous B cell lymphoma: clinical and immunohistologic characterization of four cases. J. Am. Acad. Dermatol. 1991; 24(4): 584–90.
  6. Wotherspoon A.C., Doglioni C., Diss T.C. et al. Regression of primary lowgrade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993; 342(8871): 575–7.
  7. Du M.Q., Isaccson P.G. Gastric MALT lymphoma: from aetiology to treatment. Lancet Oncol. 2002; 3(2): 97–104.
  8. Ferreri A.J., Ponzoni M., Guidoboni M. et al. Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating antibiotic therapy. J. Clin. Oncol. 2005; 23(22): 5067–73.
  9. Ferreri A.J., Govi S., Pasini E. et al. Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J. Clin. Oncol. 2012; 30(24): 2988–94.
  10. Al-Saleem T., Al-Mondhiry H. Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms. Blood 2005; 105(6): 2274–80.
  11. Anttila T.I., Lehtinen T., Leinonen M. et al. Serological evidence of an association between chlamydial infections and malignant lymphomas. Br. J. Haematol. 1998; 103(1): 150–6.
  12. Ishimatsu Y., Mukae H., Matsumoto K. et al. Two cases with pulmonary mucosa-associated lymphoid tissue lymphoma successfully treated with clarithromycin. Chest 2010; 138(3): 730–3.
  13. Fujimura M., Chin K., Sekita N. et al. Regression of mucosa-associated lymphoid tissue lymphoma of the bladder after antibiotic therapy: a case report. Hinyokika Kiyo 2008; 54(12): 783–6.
  14. Van den Bosch J., Kropman R.F., Blok P., Wijermans P.W. Disappearance of a mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder after treatment for Helicobacter pylori. Eur. J. Haematol. 2002; 68(3): 187–8.
  15. Oscier D., Bramble J., Hodges E., Wright D. Regression of mucosaassociated lymphoid tissue lymphoma of the bladder after antibiotic therapy. J. Clin. Oncol. 2002; 20(3): 882.
  16. Quinn E.R., Chan C.H., Hadlock K.G. et al. The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis. Blood 2001; 98(13): 3745–9.
  17. Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 2005; 5(4): 251–62.
  18. Martin S.W., Goodnow C.C. Burst-enhancing role of the IgG membrane tail as a molecular determinant of memory. Nat. Immunol. 2002; 3(2): 182–8.
  19. Dogan I., Bertocci B., Vilmont V. et al. Multiple layers of B cell memory with different effector functions. Nat. Immunol. 2009; 10(12): 1292–9.
  20. Vaandrager J.-W., Schuuring Ed., Kluin-Nelemans H.C. et al. DNA fiber fluorescence in situ hybridization analysis of immunoglobulin class switching in B-cell neoplasia: aberrant CH gene rearrangements in follicle center-cell lymphoma. Blood 1998; 92(8): 2871–8.
  21. Alizadeh A.A., Eisen M.B., Davis R.E. et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403(6769): 503–11.
  22. Davis R.E., Ngo V.N., Lenz G. et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010; 463(7277): 88–92.
  23. Lenz G., Nagel I., Siebert R. et al. Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma. J. Exp. Med. 2007; 204(3): 633–43.
  24. Ruminy P., Etancelin P., Couronne L. et al. The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma. Leukemia 2011; 25(4): 681–8.
  25. Klein U., Klein G., Ehlin-Henriksson B. et al. Burkitt’s lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes. Mol. Med. 1995; 1(5): 495–505.
  26. Damle R.N., Wasil T., Fais F. et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94(6): 1840–7.
  27. Hamblin T.J., Davis Z., Gardiner A. et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94(6): 1848–54.
  28. Nikitin E.A., Pivnik A.V., Sudarikov A.B. et al. A comparison of the forms of chronic lympholeukemia in relation to the mutational status of the genes of the immunoglobulin variable region. Ter. Arkh. 2000; 72(7): 52–6.
  29. Hadzidimitriou A., Agathangelidis A., Darzentas N. et al. Is there a role for antigen selection in mantle cell lymphoma? Immunogenetic support from a series of 807 cases. Blood 2011; 118(11): 3088–95.
  30. Agathangelidis A., Darzentas N., Hadzidimitriou A. et al. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood 2012; 119(19): 4467–75.
  31. Herve M., Xu K., Ng Y.S. et al. Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive B cell precursors despite expressing different antibody reactivity. J. Clin. Invest. 2005; 115(6): 1636–43.
  32. Catera R., Silverman G.J., Hatzi K. et al. Chronic lymphocytic leukemia cells recognize conserved epitopes associated with apoptosis and oxidation. Mol. Med. 2008; 14(11–12): 665–74.
  33. Chu C.C., Catera R., Zhang L. et al. Many chronic lymphocytic leukemia antibodies recognize apoptotic cells with exposed nonmuscle myosin heavy chain IIA: implications for patient outcome and cell of origin. Blood 2010; 115(19): 3907–15.
  34. Herishanu Y., Perez-Galan P., Liu D. et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood 2011; 117(2): 563–74.
  35. Duhren-von Minden M., Ubelhart R., Schneider D. et al. Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature 2012; 489(7415): 309–12.
  36. Zhu D., Ottensmeier C.H., Du M.Q. et al. Incidence of potential glycosylation sites in immunoglobulin variable regions distinguishes between subsets of Burkitt’s lymphoma and mucosa-associated lymphoid tissue lymphoma. Br. J. Haematol. 2003; 120(2): 217–22.
  37. Radcliffe C.M., Arnold J.N., Suter D.M. et al. Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor. J. Biol. Chem. 2007; 282(10): 7405–15.
  38. CoelhoV., Krysov S., Ghaemmaghami A.M. et al. Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins. PNAS 2010; 107(43): 18587–92.
  39. Sachen K.L., Strohman M.J., Singletary J. et al. Self-antigen recognition by follicular lymphoma B-cell receptors. Blood 2012; 120(20): 4182–90.
  40. Marcucci F., Mele A. Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities. Blood 2011; 117(6): 1792–8.
  41. Gisbert J.P., Garcia-Buey L., Pajares J.M. et al. Systematic review: regression of lymphoproliferative disorders after treatment for hepatitis C infection. Aliment. Pharmacol. Ther. 2005; 21(6): 653–62.
  42. Victora G.D., Nussenzweig M.C. Germinal centers. Annu. Rev. Immunol. 2012; 30: 429–57.
  43. Clark M.R., Tanaka A., Powers S.E., Veselits M. Receptors, subcellular compartments and the regulation of peripheral B cell responses: the illuminating state of anergy. Mol. Immunol. 2011; 48(11): 1281–6.
  44. Yang J., Reth M. Oligomeric organization of the B-cell antigen receptor on resting cells. Nature 2010; 467(7314): 465–9.
  45. Pierce S.K., Liu W. The tipping points in the initiation of B cell signalling: how small changes make big differences. Nat. Rev. Immunol. 2010; 10(11): 767–77.
  46. Reth M. Antigen receptor tail clue. Nature 1989; 338(6214): 383–4.
  47. Saijo K., Schmedt C., Su I.H. et al. Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development. Nat. Immunol. 2003; 4(3): 274–9.
  48. Rowley R.B., Burkhardt A.L., Chao H.G. et al. Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation motif binding and autophosphorylation. J. Biol. Chem. 1995; 270(19): 11590–4.
  49. Oellerich T., Bremes V., Neumann K. et al. The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85. EMBO J. 2011; 30(17): 3620–34.
  50. Watanabe D., Hashimoto S., Ishiai M. et al. Four tyrosine residues in phospholipase C-gamma 2, identified as BTK-dependent phosphorylation sites, are required for B cell antigen receptor-coupled calcium signaling. J. Biol. Chem. 2001; 276(42): 38595–601.
  51. Ozdener F., Dangelmaier C., Ashby B. et al. Activation of phospholipase Cgamma2 by tyrosine phosphorylation. Mol. Pharmacol. 2002; 62(3): 672–9.
  52. Shinohara H., Yasuda T., Aiba Y. et al. PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1. J. Exp. Med. 2005; 202(10): 1423–31.
  53. Coughlin J.J., Stang S.L., Dower N.A., Stone J.C. RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor-Ras signaling. J. Immunol. 2005; 175(11): 7179–84.
  54. Xu Y., Harder K.W., Huntington N.D. et al. Lyn tyrosine kinase: accentuating the positive and the negative. Immunity 2005; 22(1): 9–18.
  55. Deane J.A., Fruman D.A. Phosphoinositide 3-kinase: diverse roles in immune cell activation. Annu. Rev. Immunol. 2004; 22: 563–98.
  56. Yuan T.L., Cantley L.C. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008; 27(41): 5497–510.
  57. Laplante M., Sabatini D.M. mTOR signaling in growth control and disease. Cell 2012; 149(2): 274–93.
  58. Stone J.C. Regulation and Function of the RasGRP Family of Ras Activators in Blood Cells. Genes Cancer 2011; 2(3): 320–34.
  59. Guo B., Su T.T., Rawlings D.J. Protein kinase C family functions in B-cell activation. Curr. Opin. Immunol. 2004; 16(3): 367–73.
  60. Suzuki A., Kaisho T., Ohishi M. et al. Critical roles of PTEN in B cell homeostasis and immunoglobulin class switch recombination. J. Exp. Med. 2003; 197(5): 657–67.
  61. O’Neill S.K., Getahun A., Gauld S.B. et al. Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy. Immunity 2011; 35(5): 746–56.
  62. Pao L.I., Lam K.P., Henderson J.M. et al. B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity. Immunity 2007; 27(1): 35–48.
  63. Liu C., Bai X., Wuet J. et al. N-wasp is essential for the negative regulation of B cell receptor signaling. PLoS Biol. 2013; 11(11): e1001704.
  64. Ingley E. Src family kinases: regulation of their activities, levels and identification of new pathways. Biochim. Biophys. Acta 2008; 1784(1): 56–65.
  65. Lam K.P., Kuhn R., Rajewsky K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 1997; 90(6): 1073–83.
  66. Kraus M., Alimzhanov M.B., Rajewsky N., Rajewsky K. Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer. Cell 2004; 117(6): 787–800.
  67. Srinivasan L., Sasaki Y., Calado D.P. et al. PI3 kinase signals BCRdependent mature B cell survival. Cell 2009; 139(3): 573–86.
  68. Baracho G.V., Miletic A.V., Omori S.A. et al. Emergence of the PI3-kinase pathway as a central modulator of normal and aberrant B cell differentiation. Curr. Opin. Immunol. 2011; 23(2): 178–83.
  69. Ramadani F., Bolland D.J., Garcon F. et al. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci. Signal. 2010; 3(134): ra60.
  70. Ngo V.N., Davis R.E., Lamy L. et al. A loss-of-function RNA interference screen for molecular targets in cancer. Nature 2006; 441(7089): 106–10.
  71. Lenz G. et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 2008; 319(5870): 1676–9.
  72. Davis R.E., Davis E., Ngo V.N. et al. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J. Exp. Med. 2001; 194(12): 1861–74.
  73. Rawlings D.J., Sommer K., Moreno-Garcia M.E. The CARMA1 signalosome links the signalling machinery of adaptive and innate immunity in lymphocytes. Nat. Rev. Immunol. 2006; 6(11): 799–812.
  74. Bajpai U.D., Zhang K., Teutsch M. et al. Bruton’s tyrosine kinase links the B cell receptor to nuclear factor kappaB activation. J. Exp. Med. 2000; 191(10): 1735–44.
  75. Petro J.B., Rahman S.M.J., Ballard D.W. et al. Bruton’s tyrosine kinase is required for activation of IkappaB kinase and nuclear factor kappaB in response to B cell receptor engagement. J. Exp. Med. 2000; 191(10): 1745–54.
  76. Naylor T.L., Tang H., Ratsch B.A. et al. Protein kinase C inhibitor sotrastaurin selectively inhibits the growth of CD79 mutant diffuse large B-cell lymphomas. Cancer Res. 2011; 71(7): 2643–53.
  77. Wardemann H., Yurasov S., Schaefer A. et al. Predominant autoantibody production by early human B cell precursors. Science 2003; 301(5638): 1374–7.
  78. Gauld S.B., Benschop R.J., Merrell K.T., Cambier J.C. Maintenance of B cell anergy requires constant antigen receptor occupancy and signaling. Nat. Immunol. 2005; 6(11): 1160–7.
  79. Yarkoni Y., Getahun A., Cambier J.C. Molecular underpinning of B-cell anergy. Immunol. Rev. 2010; 237(1): 249–63.
  80. Quach T.D., Manjarrez-Orduno N., Adlowitz D.G. et al. Anergic responses characterize a large fraction of human autoreactive naive B cells expressing low levels of surface IgM. J. Immunol. 2011; 186(8): 4640–8.
  81. Smedby K.E., Hjalgrim H., Askling J. et al. Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J. Natl. Cancer Inst. 2006; 98(1): 51–60.
  82. Rui L., Schmitz R., Ceribelli M., Staudt L.M. Malignant pirates of the immune system. Nat. Immunol. 2011; 12(10): 933–40.
  83. Alfarano A., Indraccolo S., Circostaet P. et al. An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in Bchronic lymphocytic leukemia. Blood 1999; 93(7): 2327–35.
  84. Schmitz R., Young R.M., Ceribelliet M. et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature 2012; 490(7418): 116–20.
  85. Sander S., Calado D.P., Srinivasan L. et al. Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis. Cancer Cell 2012; 22(2): 167–79.
  86. Evan G.I., Wyllie A.H., Gilbert C.S. et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell 1992; 69(1): 119–28.
  87. Quesada V., Conde L., Villamor N. et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat. Genet. 2012; 44(1): 47–52.
  88. Wang L., Lawrence M.S., Wan Y. et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N. Engl. J. Med. 2011; 365(26): 2497–506.
  89. Puente X.S. et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011; 475(7354): 101–5.
  90. Amrein P.C., Attar E.C., Takvorian T. et al. Phase II study of dasatinib in relapsed or refractory chronic lymphocytic leukemia. Clin. Cancer Res. 2011; 17(9): 2977–86.
  91. Friedberg J.W., Sharman J., Sweetenham J. et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 2010; 115(13): 2578–85.
  92. Advani R.H., Buggy J.J., Sharman J.P. et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/ refractory B-cell malignancies. J. Clin. Oncol. 2013; 31(1): 88–94.
  93. Wang M.L., Rule S., Martin P. et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N. Engl. J. Med. 2013; 369(6): 507–16.
  94. Wyndham W., Gerecitano J.F., Goy A. et al. The Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the ABC subtype of relapsed/refractory de novo diffuse large B-cell lymphoma (DLBCL): interim results of a multicenter, open-label, phase 2 study. Blood (ASH Annual Meeting Abstracts) 2012; 120: 686.
  95. Byrd J.C., Furman R.R., Coutre S.E. et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 2013; 369(1): 32–42.
  96. Coutre S., Byrd J.C., Furman R.R. et al. Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia. J. Clin. Oncol. (ASCO Annual Meeting Abstracts) 2011; 29: 6631.
  97. Kahl B., Byrd J.C., Flinn I.W. et al. Clinical safety and activity in a phase 1 study of CAL-101, an isoform- selective inhibitor of phosphatidylinositol 3-kinase P110{delta}, in patients with relapsed or refractory non-Hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts) 2010; 116(21): 1777.
  98. Zent C.S., LaPlant B.R., Johnston P.B. et al. The treatment of recurrent/ refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation. Cancer 2010; 116(9): 2201–7.
  99. Renner C., Zinzani P.L., Gressin R. et al. A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma. Haematologica 2012; 97(7): 1085–91.
  100. Witzig T.E., Reeder C.B., LaPlant B.R. et al. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia 2011; 25(2): 341–7.
  101. Witzig T.E., Geyer S.M., Ghobrial I. et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J. Clin. Oncol. 2005; 23(23): 5347–56.
  102. Smith S.M., van Besien K., Karrison T. et al. Temsirolimus has activity in non-mantle cell non-Hodgkin’s lymphoma subtypes: The University of Chicago phase II consortium. J. Clin. Oncol. 2010; 28(31): 4740–6.
  103. Bruton O.C. Agammaglobulinemia. Pediatrics 1952; 9(6): 722–8.
  104. Rawlings D.J., Saffran D.C., Tsukada S. et al. Mutation of unique region of Bruton’s tyrosine kinase in immunodeficient XID mice. Science 1993; 261(5119): 358–61.
  105. Quek L.S., Bolen J., Watson S.P. A role for Bruton’s tyrosine kinase (Btk) in platelet activation by collagen. Curr. Biol. 1998; 8(20): 1137–40.
  106. Kurosaki T., Hikida M. Tyrosine kinases and their substrates in B lymphocytes. Immunol. Rev. 2009; 228(1): 132–48.
  107. Rawlings D.J., Lin S., Scharenberg A.M. et al. Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases. Science 1996; 271(5250): 822–5.
  108. Mohamed A.J., Yu L., Backesjo C.M. et al. Bruton’s tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol. Rev. 2009; 228(1): 58–73.
  109. Hantschel O., Rix U., Schmidtet U. et al. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. PNAS 2007; 104(33): 13283–8.
  110. Pan Z., Scheerens H., Li S.J. et al. Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase. Chem. Med. Chem. 2007; 2(1): 58–61.
  111. Honigberg L.A., Smith A.M., Sirisawadet M. et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc. Natl. Acad. Sci. U S A 2010; 107(29): 13075–80.
  112. Herman S.E., Gordon A.L., Hertlein E. et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 2011; 117(23): 6287–96.
  113. Ponader S., Chen Sh.-Sh., Buggy J.J. et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 2012; 119(5): 1182–9.
  114. de Rooij M.F., Kuil A., Geest C.R. et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood 2012; 119(11): 2590–4.
  115. Mocsai A., Ruland J., Tybulewicz V.L. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat. Rev. Immunol. 2010; 10(6): 387–402.
  116. Clemens G.R., Schroeder R.E., Magness S.H. et al. Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing. Birth Defects Res. Clin. Mol. Teratol. 2009; 85(2): 130–6.
  117. Braselmann S., Taylor V., Zhao H. et al. R406, an orally available spleen tyrosine kinase inhibitor blocks Fc receptor signaling and reduces immune complex-mediated inflammation. J. Pharmacol. Exp. Ther. 2006; 319(3): 998–1008.
  118. Gobessi S., Laurenti L., Longo P.G. et al. Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B cells. Leukemia 2009; 23(4): 686–97.
  119. Quiroga M.P., Balakrishnan K., Kurtova A.V. et al. B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406. Blood 2009; 114(5): 1029–37.
  120. So L., Fruman D.A. PI3K signalling in B- and T-lymphocytes: new developments and therapeutic advances. Biochem. J. 2012; 442(3): 465–81.
  121. Okkenhaug K., Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat. Rev. Immunol. 2003; 3(4): 317–30.
  122. Kloo B., Nagel D., Pfeifer M. et al. Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells. PNAS 2011; 108(1): 272–7.
  123. Rudelius M., Pittaluga S., Nishizuka S. et al. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood 2006; 108(5): 1668–76.
  124. Herman S.E., Gordon A.L., Wagner A.J. et al. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood 2010; 116(12): 2078–88.
  125. Hoellenriegel J., Meadows S.A., Sivina M. et al. The phosphoinositide 3’-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 2011; 118(13): 3603–12.
  126. Lannutti B.J., Meadows S.A., Herman S.E.M. et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 2011; 117(2): 591–4.
  127. Mattmann M.E., Stoops S.L., Lindsley C.W. Inhibition of Akt with small molecules and biologics: historical perspective and current status of the patent landscape. Expert Opin. Ther. Pat. 2011; 21(9): 1309–38.

Влияние противоопухолевого лечения на репродуктивную систему женщин: методы защиты и сохранения функции яичников

ОБЗОРЫ , , , , ,

М.В. Волочаева1, Р.Г. Шмаков1, Е.А. Демина2

1 ФГБУ «Научный центр акушерства, гинекологии и перинатологии им. В.И. Кулакова» МЗ РФ, Москва, Российская Федерация

2 ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Последние исследования показали особую важность обсуждения вопроса защиты и сохранения функции яичников у женщин с онкологическими заболеваниями. В настоящее время, когда созданы во многом эффективные схемы лечения злокачественных опухолей, для ряда больных становится актуальным продолжение полноценной жизни после успешной противоопухолевой терапии. В обзоре рассматриваются методики защиты и сохранения функции яичников: фармакологическая, c применением вспомогательных репродуктивных технологий, в т. ч. криоконсервации и трансплантация ткани яичников, криоконсервации ооцитов и эмбрионов.

Ключевые слова: защита яичников, cохранение функции яичников, рак, криоконсервация ткани, криоконсервация ооцитов, криоконсервация эмбрионов.

Читать  стать в PDFpdficon

 ЛИТЕРАТУРА

  1. Демина Е.А., Махова Е.Е., Сусулева Н.А., Ильященко В.А. Возможности сохранения детородной функции у женщин с лимфомой Ходжкина. РМЖ 2005; 1: 26–8.[Demina Ye.A., Makhova Ye.Ye., Susuleva N.A., and Ilyashchenko V.A. Potentials for preservation of reproductive function in females with Hodgkin’s lymphoma. RMZh 2005: 1:26–8. (In Russ.)].
  2. Шмаков Р.Г. Репродуктивное здоровье женщин с онкогематологическими заболеваниями: Автореф. дис. … д-ра мед. наук. М., 2008.[Shmakov R.G. Reproduktivnoye zdorove zhenshchin s onkogematologicheskimi zabolevaniyami. Dokt. diss. (Reproductive health in women with hematological malignancies : Dr. med. sci. diss.). M., 2008.]
  3. Maltaris T., Seufert R., Fischl F. et al. The effect of cancer treatment on female fertility and strategies for preserving fertility. Eur. J. Obstet. Gynecol. Reprod. Biol. 2007; 130: 148–55.
  4. Blumenfeld Z. Ovarian rescue/protection from chemotherapeutic agents. J. Soc. Gynecol. Investig. 2001; 8: 60–4.
  5. Blumenfeld Z. Reservation of fertility and ovarian function and minimalization of chemotherapy associated gonadotoxicity and premature ovarian failure: the role of inhibin-A and -B as markers. Mol. Cell. Endocrinol. 2002; 187: 93–105.
  6. Minton S.E., Munster P.N. Chemotherapy-induced amenorrhea and fertility in women undergoing adjuvant treatment for breast cancer. Cancer Control 2002; 9: 466–72.
  7. Mrozek E., Shapiro C.L. Survivorship and complications of treatment in breast cancer. Clin. Adv. Hematol. Oncol. 2005; 3: 211–22.
  8. Friedman D.L., Constine L.S. Late effects of treatment for Hodgkin lymphoma. J. Natl. Compr. Cancer Network 2006; 4: 249–57.
  9. Haukvik U.K., Dieset I., Bjoro T. et al. Treatment-related premature ovarian failure as a long-term complication after Hodgkin’s lymphoma. Ann. Oncol. 2006; 17: 1428–33.
  10. Behringer K., Mueller H., Goergen H. et al. Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J. Clin. Oncol. 2013; 31: 231–9.
  11. De Bruin M.L., Huisbrink J., Hauptmann M. et al. Treatment-related risk factors for premature menopause following Hodgkin lymphoma. Blood 2008; 111: 101–8.
  12. Van der Kaaij M.A., van Echten-Arends J., Simons A.H. et al. Fertility preservation after chemotherapy for Hodgkin lymphoma. Hematol. Oncol. 2010; 28: 168–79.
  13. Fornier M.N., Modi S., Panageas K.S. et al. Incidence of chemotherapy induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane. Cancer 2005; 104: 1575–9.
  14. Behringer K., Breuer K., Reineke T. et al. Secondary amenorrhea after Hodgkin’s lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin’s Lymphoma Study Group. J. Clin. Oncol. 2005; 23: 7555–64.
  15. Gerber B., Dieterich M., Muеller H. et al. Controversies in preservation of ovary function and fertility in patients with breast cancer. Breast Cancer Res. Treat. 2008; 108: 1–7.
  16. Okanami Y., Ito Y., Watanabe C. et al. Incidence of chemotherapy induced amenorrhea in premenopausal patients with breast cancer following adjuvant anthracycline and taxane. Breast Cancer 2011; 18: 182–8.
  17. Lee S.J., Schover L.R., Partridge A.H. et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J. Clin. Oncol. 2006; 24: 2917–31.
  18. Tham Y.L., Sexton K., Weiss H. et al. The rates of chemotherapy induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane. Am. J. Clin. Oncol. 2007; 30: 126–32.
  19. Sklar C.A., Mertens A.C., Mitby P. et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J. Natl. Cancer Inst. 2006; 98: 890–6.
  20. Dillon K.E., Sammel M.D., Prewitt M. et al. Pretreatment antimullerian hormone levels determine rate of post therapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy. Fertil. Steril. 2013; 99: 477–83.
  21. Wallace W.H., Thomson A.B., Saran F. et al. Predicting age of ovarian failure after radiation to a field that includes the ovaries. Int. J. Radiat. Oncol. Biol. Phys. 2005; 62: 738–44.
  22. Knauff E.A., Eijkemans M.J., Lambalk C.B. et al. Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J. Clin. Endocrinol. Metab. 2009; 94: 786–92.
  23. Iwase A., Sugita A., Hirokawa W. et al. Anti-Mullerian hormone as a marker of ovarian reserve following chemotherapy in patients with gestational trophoblastic neoplasia. Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 167: 194–8.
  24. Munster P.N., Moore A.P., Ismail-Khan R. et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. J. Clin. Oncol. 2012; 30: 533–8.
  25. Recchia F., Saggio G., Amiconi G. et al. Gonadotropin-releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma. Cancer 2006; 106: 514–23.
  26. Han S.S., Kim Y.H., Lee S.H. et al. Underuse of ovarian transposition in reproductive-aged cancer patients treated by primary or adjuvant pelvic irradiation. J. Obstet. Gynaecol. Res. 2011; 37: 825–9.
  27. Pentheroudakis G., Pavlidis N., Castiglione M. Cancer, fertility and pregnancy: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann. Oncol. 2009; 20: 178–81 (Suppl. 4).
  28. Donnez J., Dolmans M.M. Cryopreservation and transplantation of ovarian tissue. Clin. Obstet. Gynecol. 2010; 53: 787–96.
  29. Bedaiwy M.A., Abou-Setta A.M., Desai N. et al. Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: A systematic review and meta-analysis. Fertil. Steril. 2011; 95: 906–14, e1–4.
  30. Blumenfeld Z., von Wolff M. GnRH analogues and oral contraceptives for fertility preservation in women during chemotherapy. Hum. Reprod. Update 2008; 14: 543–52.
  31. Демина Е.А., Перилова Е.Е., Шмаков Р.Г. Использование комбинированных пероральных контрацептивов для профилактики повреждения функции яичников у больных лимфомой Ходжкина. М., 2004: 1352–4. [Demina Ye.A., Perilova Ye.Ye., Shmakov R.G. Ispolzovaniye kombinirovannykh peroralnykh kontratseptivov dlya profilaktiki povrezhdeniya funktsii yaichnikov u bolnykh limfomoy Khodzhkina (Use of oral contraceptives for prevention of ovarian function damage in patients with Hodgkin’s lymphoma). M., 2004: 1352–4.]
  32. Blumenfeld Z., Avivi I., Linn S. et al. Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. Hum. Reprod. 1996; 11: 1620–6.
  33. Badawy A., Elnashar A., El-Ashry M. et al. Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. Fertil. Steril. 2009; 91: 694–7.
  34. Sverrisdottir A., Nystedt M., Johansson H. et al. Adjuvant goserelin and ovarian preservation in chemotherapy treated patients with early breast cancer: results from a randomized trial. Breast Cancer Res. Treat. 2009; 117: 561–7.
  35. Clowse M.E., Behera M.A., Anders C.K. et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J. Womens Health 2009; 18: 311–9.
  36. Del Mastro L., Boni L., Michelotti A. et al. Effect of the gonadotropinreleasing hormone analogue triptorelin on the occurrence of chemotherapyinduced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA 2011; 306: 269–76.
  37. Chen H., Li J., Cui T. et al. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev 2011; 9: CD008018.
  38. Wong M., O’Neill S., Walsh G. et al. Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes. Ann. Oncol. 2013; 24: 133–8.
  39. Yang B., Shi W., Yang J. et al. Concurrent treatment with gonadotropinreleasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: A meta-analysis of randomized controlled trials. Breast 2013; 22: 150–7.
  40. Leonard R.C., Adamson D., Anderson R. et al. The OPTION trial of adjuvant ovarian protection by goserelin in adjuvant chemotherapy for early breast cancer. J. Clin. Oncol. 2010; 28: Abstract 590.
  41. Gerber B., von Minckwitz G., Stehle H. et al. Effect of luteinizing hormonereleasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study. J. Clin. Oncol. 2011; 29: 2334–41.
  42. Elgindy E.A., El-Haieg D.O., Khorshid O.M. et al. Gonadatrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial. Obstet. Gynecol. 2013; 121: 78–86.
  43. American Society for Reproductive Medicine. http://www.asrm.org
  44. Azim A.A., Costantini-Ferrando M., Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: A prospective controlled study. J. Clin. Oncol. 2008; 26: 2630–5.
  45. Oktay K., Buyuk E., Libertella N. et al. Fertility preservation in breast cancer patients: A prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J. Clin. Oncol. 2005; 23: 4347–53.
  46. Lee S., Oktay K. Does higher starting dose of FSH stimulation with letrozole improve fertility preservation outcomes in women with breast cancer? Fertil. Steril. 2012; 98: 961.e1–4.e1.
  47. Sonmezer M., Turkcuoglu I., Coskun U., Oktay K. Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles. Fertil. Steril. 2011; 95: 2125.e9–11.
  48. Isachenko V., Isachenko E., Keck G. et al. First live birth in Germany after re-transplantation of cryopreserved ovarian tissue: Original device for initiation of ice formation. Clin. Lab. 2012; 58: 933–8.
  49. Bacigalupo A., Ballen K., Rizzo D. et al. Defining the intensity of conditioning regimens: Working definitions. Biol. Blood Marrow Transplant. 2009; 15: 1628–33.
  50. Borini A., Bianchi V. Cryopreservation of mature and immature oocytes. Clin. Obstet. Gynecol. 2010; 53: 763–74.
  51. Huang J.Y., Chian R.C., Gilbert L. et al. Retrieval of immature oocytes from unstimulated ovaries followed by in vitro maturation and vitrification: A novel strategy of fertility preservation for breast cancer patients. Am. J. Surg. 2010; 200: 177–83.
  52. Rudick B., Opper N., Paulson R. et al. The status of oocyte cryopreservation in the United States. Fertil. Steril. 2010; 94: 2642–6.
  53. Demeestere I., Simon P., Emiliani S., Delbaere A., Englert Y. Orthotopic and heterotopic ovarian tissue transplantation. Hum. Reprod. Update 2009; 15: 649–65.
  54. Demeestere I., Moffa F., Peccatori F., Poirot C., Shalom-Paz E. Multiple approaches for individualized fertility protective therapy in cancer patients. Obstet. Gynecol. Int. 2012: 495142 (Medline Abstract).
  55. Oktay K., Cil A.P., Bang H. Efficiency of oocyte cryopreservation: A metaanalysis. Fertil. Steril. 2006; 86: 70–80.
  56. Donnez J., Squifflet J., Jadoul P. et al. Pregnancy and live birth after autotransplantation of frozen-thawed ovarian tissue in a patient with metastatic disease undergoing chemotherapy and hematopoietic stem cell transplantation. Fertil. Steril. 2011; 95: 1787.e1–4.
  57. Kim M.K., Lee D.R., Han J.E. et al. Live birth with vitrified-warmed oocytes of a chronic myeloid leukemia patient nine years after allogenic bone marrow transplantation. J. Assist. Reprod. Genet. 2011; 28: 1167–70.
  58. Dittrich R., Lotz L., Keck G. et al. Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation. Fertil. Steril. 2012; 97: 387–90.
  59. Andersen C.Y., Silber S.J., Berghold S.H. et al. Long-term duration of function of ovarian tissue transplants: Case reports. Reprod. Biomed. Online 2012; 25: 128–32.
  60. Oktay K., Rodriguez-Wallberg K.A. Four spontaneous pregnancies and three live births following subcutaneous transplantation of frozen banked ovarian tissue: What is the explanation? Fertil. Steril. 2011; 95: 804.e7–10.
  61. Meirow D., Levron J., Eldar-Geva T. et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N. Engl. J. Med. 2005; 353: 318–21.
  62. Anderson R.A., Wallace W.H., Baird D.T. Ovarian cryopreservation for fertility preservation: Indications and outcomes. Reproduction 2008; 136: 681–9.
  63. Reebals J.F., Brown R., Buckner E.B. Nurse practice issues regarding sperm banking in adolescent male cancer patients. J. Pediatr. Oncol. Nurs. 2006; 23: 182–8.
  64. Keros V., Hultenby K., Borgstrumlom B. et al. Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Hum. Reprod. 2007; 22: 1384–95.
  65. Jadoul P., Dolmans M.M., Donnez J. Fertility preservation in girls during childhood: Is it feasible, efficient and safe and to whom should it be proposed? Hum. Reprod. Update 2010; 16: 617–30.
  66. Cvancarova M., Samuelsen S.O., Magelssen H. et al. Reproduction rates after cancer treatment: Experience from the Norwegian radium hospital. J. Clin. Oncol. 2009; 27: 334–43.
  67. Nieman C.L., Kinahan K.E., Yount S.E. et al. Fertility preservation and adolescent cancer patients: Lessons from adult survivors of childhood cancer and their parents. Cancer Treat. Res. 2007; 138: 201–17

Аутофагия: клеточная гибель или способ выживания?

ОБЗОРЫ , ,

О.В. Ковалева, М.С. Шитова, И.Б. Зборовская

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Взаимодействие процессов пролиферации, дифференцировки и гибели клеток служит неотъемлемой частью жизнедеятельности многоклеточных организмов. Нарушение баланса между этими процессами лежит в основе развития многих заболеваний человека. Понимание их молекулярных механизмов необходимо для поиска новых диагностических и терапевтических мишеней. В последнее десятилетие большой интерес у ученых вызывает процесс аутофагии и ее роль в жизнедеятельности клетки как в норме, так и при патологии. Аутофагия — это процесс утилизации клеточных органелл и макромолекул. Аутофагия сопровождает жизнедеятельность любой нормальной клетки в обычных условиях. Однако при определенных обстоятельствах аутофагия может приводить к клеточной гибели. Нарушения аутофагии играют роль в развитии онкологических, мышечных и нейродегенеративных заболеваний, кардиомиопатии и др.

Ключевые слова: апоптоз, аутофагия, канцерогенез

Читать статью в PDFpdficon

ЛИТЕРАТУРА

  1. Galluzzi L., Vitale I., Abrams J.M. et al. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ. 2012; 19(1): 107–20.
  2. Kerr J.F., Wyllie A.H., Currie A.R. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 1972; 26: 239–57.
  3. Wong R.S. Apoptosis in cancer: from pathogenesis to treatment. J. Exp. Clin. Cancer Res. 2011; 26: 30–87.
  4. Hu Y., Benedict M.A., Ding L., Nunez G. Role of cytochrome c and dATP/ ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J. 1999; 18: 3586–95.
  5. Saelens X., Festjens N., Vande Walle L. et al. Toxic proteins released from mitochondria in cell death. Oncogene 2004; 23(16): 2861–74.
  6. Altieri D.C. Surviving in apoptosis control and cell cycle regulation in cancer. Prog. Cell Cycle Res. 2003; 5: 447–52.
  7. Tamm I., Wang Y., Sausville E. et al. IAP-family protein surviving inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 1998; 58(23): 5315–20.
  8. Padanilam B.J. Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis. Am. J. Physiol. Renal. Physiol. 2003; 284(4): F608–27.
  9. Hoste E., Kemperman P., Devos M. et al. Caspase-14 is required for filaggrin degradation to natural moisturizing factors in the skin. J. Invest. Dermatol. 2011; 131(11): 2233–41.
  10. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 2004; 6(4): 463–77.
  11. Okada H., Mak T.W. Pathways of apoptotic and non-apoptotic death in tumor cells. Nat. Rev. Cancer 2004; 4(8): 592–603.
  12. Kaminskyy V., Zhivotovsky B. Proteases in autophagy. Biochimica er Biophysica Acta. 2012; 1824: 44–50.
  13. Mijaljica D., Prescott M., Devenish R.J. Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum. Autophagy 2011; 7: 673–82.
  14. Klionsky DJ., Codogno P., Cuervo A.M. et al. A comprehensive glossary of autophagy-related molecules and processes. Autophagy 2010; 6(4): 438–48.
  15. Massey A.C., Zhang C., Cuervo A.M. Chaperone-mediated autophagy in aging and disease. Curr. Top. Dev. Biol. 2006; 73: 205–35.
  16. Kimmelman A.C. The dynamic nature of autophagy in cancer. Genes Dev. 2011; 25(19): 1999–2010.
  17. Reggiori F., Tucker K.A., Stromhaug P.E., Klionsky D.J. The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev. Cell 2004; 6(1): 79–90.
  18. Wang C.W., Klionsky D.J. The molecular mechanism of autophagy. Mol. Med. 2003; 9: 65–76.
  19. Teter S.A., Klionsky D.J. Transport of proteins to the yeast vacuole: autophagy, cytoplasm-to-vacuole targeting, and role of the vacuole in degradation. Semin. Cell Dev. Biol. 2000; 11(3): 173–9.
  20. Chen N., Debnath J. Autophagy and Tumorigenesis. FEBS Lett. 2010; 584(7): 1427–35.
  21. Guertin D.A., Sabatini D.M. Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9–22.
  22. He C., Klionsky D.J. Regulation Mechanisms and Signaling Pathways of Autophagy. Annu. Rev. Genet. 2009; 43: 67–93.
  23. Zhou H., Huang S. The complexes of mammalian target of rapamycin. Curr. Protein Pept. Sci. 2010; 11: 409–24.
  24. Teter T., Hall M.N. TOR, a central controller of cell growth. Cell 2000; 103(2): 253–62.
  25. Tee A.R., Manning B.D., Roux P.P., Cantley L.C., Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr. Biol. 2003; 13: 1259–68.
  26. Shackelford D.B., Shaw R.J. The LKB1-AMPK pathway: metabolism and growth control in tumor suppression. Nat. Rev. Cancer 2009; 9: 563–75.
  27. Liang J., Shao SH., Xu Z.X. et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat. Cell Biol. 2007; 9: 218–24.
  28. Feng Z., Hu W., Stanchina E. et al. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res. 2007; 67: 3043–53.
  29. Mortensen M., Watson A.S., Simon A.K. Lack of autophagy in the hematopoietic system leads to loss of hematopoietic stem cell function and dysregulated myeloid proliferation. Autophagy 2011; 7(9): 1069–70.
  30. Mortensen M., Soilleux E.J., Djordjevic G. et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J. Exp. Med. 2011; 208: 455–67.
  31. Pua H.H., Komatsu M., He Y.W. Autophagy is essential for mitochondrial clearance in mature T lymphocytes. J. Immunol. 2009; 182: 4046–55.
  32. Pua H.H., Dzhagalov I., Chuck M. et al. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J. Exp. Med. 2007; 204: 25–31.
  33. Pua H.H., He Y.W. Maintaining T lymphocyte homeostasis: another duty of autophagy. Autophagy 2007; 3: 266–7.
  34. Miller B.C., Zhao Z., Stephenson L.M. et al. The autophagy gene Atg5 plays an essential role in B lymphocyte development. Autophagy 2008; 4: 309–14.
  35. Novak I., Kirkin V., McEwan D.G. et al. Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep. 2010; 11(1): 45–51.
  36. Kundu M., Lindsten T., Yang C.Y. et al. Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation. Blood 2008; 112: 1493–502.
  37. Raslova H., Kauffmann A., Sekkai D. et al. Interrelation between polyploidization and megakaryocyte differentiation: a gene profiling approach. Blood. 2007; 109: 3225–34.
  38. Delgado M.A., Elmaoued R.A., Davis A.S., Kyei G., Deretic V. Toll-like receptors control autophagy. EMBO J. 2008; 27: 1110–21.
  39. Shi C.S., Kehrl J.H. MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J. Biol. Chem. 2008; 283: 33175–82.
  40. Xu Y., Jagannath C., Liu X.D. et al. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity. 2007; 27: 135–44.
  41. Канцерогенез. Под ред. Д.Г. Заридзе. М.: Медицина, 2004. [Kantserogenez. Pod red. D.G. Zaridze (Carcinogenesis. Ed. by: D.G. Zaridze). M.: Meditsina, 2004.]
  42. Liang X.H., Jackson S., Seaman M. et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672–6.
  43. Yue Z., Jin S., Yang C., Levine A.J., Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. U S A 2003; 100: 15077–82.
  44. Qu X., Yu J., Bhagat G. et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 2003; 112: 1809–20.
  45. Karantza-Wadsworth V., Patel S., Kravchuk O. et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 2007; 21: 1621–35.
  46. Meek D.W. Tumor suppression by p53: a role for the DNA damage response? Nat. Rev. Cancer 2009; 9: 714–23.
  47. Degenhardt K., Mathew R., Beaudoin B. et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006; 10: 51–64.
  48. DeNardo D., Johansson M., Coussens L. Immune cells as mediators of solid tumor metastasis. Cancer Metast. Rev. 2008; 27: 11–8.
  49. DeNardo D.G., Barreto J.B., Andreu P. et al. CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages. Cancer Cell 2009; 16: 91–102.
  50. Bingle L., Brown N.J., Lewis C.E. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J. Pathol. 2002; 196: 254–65.
  51. Young A.R., Narita M., Ferreira M. et al. Autophagy mediates the mitotic senescence transition. Genes Dev. 2009; 23: 798–803.
  52. Petiot A., Ogier-Denis E., Blommaart E.F., Meijer AJ., Codogno P. Distinct classes of phosphatidylinositol 3¢-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J. Biol. Chem. 2000; 275: 992–8.
  53. Luiken J.J., Aerts J.M., Meijer A.J. The role of the intralysosomal pH in the control of autophagic proteolytic flux in rat hepatocytes. Eur. J. Biochem. 1996; 235: 564–73.
  54. Yamamoto A., Tagawa Y., Yoshimori T. et al. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct. Funct. 1998; 23: 33–42.
  55. Ito H., Daido S., Kanzawa T., Kondo S., Kondo Y. Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int. J. Oncol. 2005; 26: 1401–10.
  56. Lomonaco S.L., Finniss S., Xiang C. et al. The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells. Int. J. Cancer 2009; 125: 717–22.
  57. Shingu T., Fujiwara K., Bogler O. et al. Stage-specific effect of inhibition of autophagy on chemotherapy-induced cytotoxicity. Autophagy 2009; 5: 537–9.
  58. Vazquez-Martin A., Oliveras-Ferraros C., Menendez J.A. Autophagy facilitates the development of breast cancer resistance to the anti-HER2 monoclonal antibody trastuzumab. PLoS One 2009; 4: e6251.
  59. Abedin M.J., Wang D., McDonnell M.A., Lehmann U., Kelekar A. Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death Differ. 2007; 14: 500–10.
  60. Kim R.H., Coates J.M., Bowles T.L. et al. Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Res. 2009; 69: 700–8.
  61. Bellodi C., Lidonnici M.R., Hamilton A. et al. Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosomepositive cells, including primary CML stem cells. J. Clin. Invest. 2009; 119: 1109–23.
  62. Carew J.S., Nawrocki S.T., Kahue C.N. et al. Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl-mediated drug resistance. Blood 2007; 10: 313–22.
  63. Ertmer A., Huber V., Gilch S. et al. The anticancer drug imatinib induces cellular autophagy. Leukemia 2007; 21: 936–42.
  64. Kamitsuji Y., Kuroda J., Kimura S. et al. The Bcr-Abl kinase inhibitor INNO-406 induces autophagy and different modes of cell death execution in Bcr-Abl-positive leukemias. Cell Death Differ. 2008; 15: 1712–22.
  65. Goussetis D.J., Altman J.K., Glaser H. et al. Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide. J. Biol. Chem. 2010; 285: 29989–97.
  66. Qian W., Liu J., Jin J. et al. Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via up-regulation of Beclin-1. Leuk. Res. 2007; 31: 329–39.
  67. Charoensuk V., Gati WP., Weinfeld M. et al. Differential cytotoxic effects of arsenic compounds in human acute promyelocytic leukemia cells. Toxicol. Appl. Pharmacol. 2009; 239: 64–70.
  68. Chiarini F., Grimaldi C., Ricci F. et al. Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVPBEZ235 against T-cell acute lymphoblastic leukemia. Cancer Res. 2010; 70: 8097–107.
  69. Crazzolara R., Bradstock K.F., Bendall L.J. RAD001 (everolimus) induces autophagy in acute lymphoblastic leukemia. Autophagy 2009; 5: 727–8.
  70. Crazzolara R., Cisterne A., Thien M. et al. Potentiating effects of RAD001 (everolimus) on vincristine therapy in childhood acute lymphoblastic leukemia. Blood 2009; 113: 3297–306.
  71. Puissant A., Auberger P. AMPK- and p62/SQSTM1-dependent autophagy mediate resveratrol-induced cell death in chronic myelogenous leukemia. Autophagy 2010; 6(5): 655–7.
  72. Puissant A., Robert G., Fenouille N. et al. Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK mediated p62/SQSTM1 expression and AMPK activation. Cancer Res. 2010; 70: 1042–52.
  73. Kroemer G., Levine B. Autophagic cell death: the story of a misnomer. Nat. Rev. Mol. Cell Biol. 2008; 9: 1004–10.
  74. Turcotte S., Chan D.A., Sutphin P.D. et al. A molecule targeting VHLdeficient renal cell carcinoma that induces autophagy. Cancer Cell. 2008; 14: 90–102.
  75. Kanzawa T., Germano I.M., Komata T. et al. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 2004; 11: 448–57.

Модель миелофиброза in vitro с использованием тромболизата человека

ОБЗОРЫ , , ,

Е.Н. Булычева, Н.Т. Сиордия, Е.Г. Ломаиа, А.Ю. Зарицкий, П.А. Бутылин

ФГБУ «ФЦСКЭ им. В.А. Алмазова», Санкт-Петербург, Российская Федерация

РЕФЕРАТ

Разработка и изучение модели миелофиброза in vitro — актуальный вопрос, решение которого позволит выявить механизмы развития заболевания и потенциальные мишени для терапии.

Целью работы было изучить свойства мезенхимных стволовых клеток (МСК) при их культивировании с использованием тромболизата от пациентов и здоровых доноров.

Пациенты и методы. МСК от здоровых доноров и пациентов с первичным миелофиброзом (ПМФ) культивировали на средах с тромболизатом (ТЛ) различной концентрации. Оценивали пролиферативную активность МСК, экспрессию белков внеклеточного матрикса, способность к остеогенной и адипогенной дифференцировке. Концентрацию ростовых факторов (bFGF, VEGF, TGF-b, HGF) в ТЛ от 17 пациентов c ПМФ (n = 14) и постполицитемическим миелофиброзом (n = 3) измеряли с помощью иммуноферментного анализа.

Результаты. Пролиферативная активность МСК, культивированных на ТЛ высокой концентрации (10–20 %), статистически значимо не отличалась от контрольных условий. Отношение экспрессии гена коллагена III типа к коллагену I типа было максимальным при использовании 10% ТЛ. Использование ТЛ для культивирования МСК не приводило к изменению их способности к дифференцировке в остеогенном направлении, но при повышении концентрации ТЛ способность к адипогенной дифференцировке снижалась. Концентрации bFGF и VEGF в ТЛ от больных были статистически значимо выше, чем в контрольной группы (в 2,5 и 2,4 раза соответственно; p < 0,01). Концентрация TGF-b и HGF имела тенденцию к повышению, но статистически значимо не отличалась от контрольной группы (p = 0,2). Культивирование МСК на ТЛ от пациентов с миелофиброзом приводило к увеличению их пролиферативной активности. МСК от больных ПМФ в определенной степени усиливали пролиферацию при культивировании на ТЛ по сравнению с МСК от здоровых доноров.

Выводы. Культивирование МСК на ТЛ может быть использовано как адекватная модель миелофиброза in vitro, т. к. приводит к профибротическим изменениям клеток стромы костного мозга.

Ключевые слова: первичный миелофиброз, тромболизат, мезенхимные стволовые клетки, модель миелофиброза in vitro.

Читать статью в PDFpdficon

Литература

  1. Kutti J., Ridell B. Epidemiology of the myeloproliferative disorders: essential thrombocythaemia, polycythaemia vera and idiopathic myelofibrosis. Biol. 2001; 49: 164–6.
  2. Johansson P., Kutti J., Andreasson B. et al. Trends in the incidence of chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders in the city of Goteborg, Sweden, during 1983–99. Inter. Med. 2004; 256: 161–5.
  3. Cervantes F., Dupriez B., Passamonti F. et al. Improving survival trends in primary myelofibrosis: an international study. Clin. Oncol. 2012; 30: 2981–7.
  4. Barosi G., Ambrosetti A., Finelli C. et al. The Italian Consensus Conferen ce on Diagnostic Criteria for Myelofibrosis with Myeloid Metaplasia. J. Haematol. 1999; 104(4): 730–7.
  5. Колосков А.В. Мегакариоциты и фиброз костного мозга. Гематол. и трансфузиол. 1997; 42: 29–31. [Koloskov A.V. Megakariotsity i fibroz kostnogo mozga (Megakaryocytes and bone marrow fibrosis. In: Hematol. & transfuziol.). Gematol. i transfuziol. 1997; 42: 29–31.]
  6. Reilly J.T. Idiopathic myelofibrosis: pathogenesis to treatment. Oncol. 2006; 24: 56–63.
  7. Le Bousse-Kerdiles M.-C., Martyre M.-C., Samson M. Cellular and molecular mechanisms underlying bone marrow and liver fibrosis: a review. Cytokine Netw. 2008; 19: 69–80.
  8. Yan X.Q., Lacey D., Fletcher F. et al. Chronic exposure to retroviral encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice. Blood 1995; 86; 4025–33.
  9. Vannucchi A.M., Bianchi L., Paoleti F. et al. Impaired GATA-1 expression and myelofibrosis in an animal model. Biol. 2004; 52: 275–9.
  10. Xing S., Wanting T.H., Zhao W. et al. Transgenic expression of Jak2V617F causes myeloproliferative disorders in mice. Blood 2008; 111: 5109–17.
  11. Wernig G., Mercher T., Okabe R. et al. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 2006; 107: 4274–81.
  12. Kirabo A., Park S.O., Wamsley H.L. et al. The small molecule inhibitor G6 significantly reduces bone marrow fibrosis and the mutant burden in a mouse model of Jak2-mediated myelofibrosis. AJP 2012; 181: 858–65.
  13. Triviai I., Stubing Th., Niebuhr B. et al. A mouse model for human myelofibrosis. 18th Congress of EHA 2013: Abstract P248.
  14. Xia W., Li H., Wang Zh. et al. Human platelet lysate supports ex vivo expansion and enhances osteogenic differentiation of human bone
  15. Sankaranarayanan K., Chandana T., Gency Ponrose G. et al. Humanized substitutes for animal sera in human mesenchymal stem cell culture and differentiation. Cell Biol. Intern. 2011; Manuscript CBI20100649.
  16. Jenhani F., Durand V., Ben Azouna N. et al. Human cytokine expression profile in various conditioned media for in vitro expansion bone marrow and umbilical cord blood immunophenotyped mesenchymal stem cells. Proceed. 2011; 43: 639–43.
  17. Doucet Ch., Ernou I., Zhang Y. et al. Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. Cell. Physiol. 2005; 205: 228–36.
  18. Horn P., Bokermann G., Cholewa D. et al. Impact of individual platelet lysates on isolation and growth of human mesenchymal stromal cells. Cytotherapy 2010; 12: 888–98.
  19. Schmitt A., Jouault H., Guichard J. et al. Pathologic interaction between megacaryocytes and polymorphonuclear leukocytes in myelofibrosis. Blood 2000; 96: 1342–7.

 

Прошлое и настоящее лучевой терапии в онкологии

ОБЗОРЫ , , ,

О.П. Трофимова, С.И. Ткачев, Т.В. Юрьева

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

В статье отражены этапы становления и развития лучевой терапии злокачественных опухолей различных локализаций — от открытия Х-лучей В.К. Рентгеном до использования искусственного изотопа 60Со, создания линейных ускорителей электронов. В настоящее время около 70 % онкологических больных нуждаются в проведении лучевой терапии на том или ином этапе противоопухолевого лечения. Усовершенствование технологии для проведения лучевой терапии, разработка новых методик облучения позволяют решить основную задачу — разрушение опухоли с минимальным лучевым воздействием на окружающие ее нормальные ткани. В работе описаны способы проведения лучевой терапии, подробно представлены отличия конвенциональной и конформной лучевой терапии. Освещены этапы предлучевой подготовки пациентов. Даны характеристики различных технологий конформной лучевой терапии.

Ключевые слова: радиоактивное излучение, лучевая терапия, предлучевая подготовка, линейный ускоритель электронов.

Читать статью в PDFpdficon

Литература 

  1. Гернек Ф. Пионеры атомного века. Великие исследователи от Максвелла до Гейзенберга. М.: Прогресс, 1974.  [Gernek F. Pionery atomnogo veka. Velikiye issledovateli ot Maksvella do Geyzenberga (Pioneers of atomic age. Great explorers from Maxwell to Heisenberg). M.: Progress, 1974.]
  2. Труфанов Г.Е., Асатурян М.А., Жаринов Г.М. Лучевая терапия (учебник для вузов). М.: ГЭОТАР-Медиа, 2007. Т. 2. [Trufanov G.E., Asaturyan M.A., Zharinov G.M. Luchevaya terapiya (uchebnik dlya vuzov) (Radiotherapy (manual for medical institutes)). M.: GEOTAR-Media, 2007. Vol. 2.]
  3. Grubbe E.H. Priority in the therapeutic use of X-Rays. Radiology 1933: 156–62.
  4. Hoffman R., Furie B., McGlave Ph. et al. Hematology: Basic Principles and Practice, 5th edn. Churchill Livingstone, 2008: 2560.
  5. Козлова А.В. Лучевая терапия злокачественных опухолей. М., 1971. [Kozlova A.V. Luchevaya terapiya zlokachestvennykh opukholey (Radiotherapy for malignant tumors). M., 1971.]
  6. Chao А., Tigner M. Handbook of Accelerator Physics and Engineering, 1999.
  7. Ткачев С.И., Нечушкин М.И., Юрьева Т.В. Современные возможности лучевой терапии злокачественных опухолей. Вестн. РАМН 2011; 12: 34–40.  [Tkachev S.I., Nechushkin M.I., Yuryeva T.V. Sovremennyye vozmozhnosti luchevoy terapii zlokachestvennykh opukholey (Current potentialities of radiotherapy for malignant tumors. In: Bull. of RAMS). Vestn. RAMN 2011; 12: 34–40.]
  8. Юрьева Т.В., Ратнер Т.Г., Сахаровская В.Г. Оценка качества рентге- новского симулятора с функцией компьютерной томографии. Сб. мат-лов III Евразийского конгресса по медицинской физике и инженерии «Меди- цинская физика — 2010». М., 2010; 2: 343–5. [Yuryeva T.V., Ratner T.G., Sakharovskaya V.G. Otsenka kachestva rentgenovskogo simulyatora s funktsiyey kompyuternoy tomografii. Sb. mat-lov III Yevraziyskogo kongressa po meditsinskoy fizike i inzhenerii «Meditsinskaya fizika — 2010» (Assessment of quality of X-ray simulator with computed tomography function. Coll. of materials of 3rd Eurasian congress on medical physics and engineering “Medical physics — 2010”). M., 2010; 2: 343–5.]
  9. Favier O., Heutte N., Stamatoullas-Bastard A. Survival after Hodgkin lymphoma: causes of death and excess mortality in patients treated in 8 consecutive trials. Cancer 2009; 115(8): 1680–91.
  10. Переслегин И.А., Саркисян Ю.Х. Клиническая радиология. М., 1973. [Pereslegin I.A., Sarkisyan Yu.Kh. Klinicheskaya radiologiya (Clinical radiology). M., 1973.]
  11. Артемова Н.А., Минайло И.И., Страх А.Г. Объемное планирование лучевой терапии. Мед. новости 2005; 11: 5–10. [Artemova N.A., Minaylo I.I., Strakh A.G. Obyemnoye planirovaniye luchevoy terapii (Three dimensional planning in radiotherapy. In: Med. news). Med. novosti 2005; 11: 5–10.]
  12. Артемова Н.А., Минайло И.И., Страх А.Г. Предлучевая подготовка с использованием объемного планирования. В сб.: Контроль качества лучевой терапии и лучевой диагностики. Минск, 2009: 261–70. [Artemova N.A., Minaylo I.I., Strakh A.G. Predluchevaya podgotovka s ispolzovaniyem obyemnogo planirovaniya. V sb.: Kontrol kachestva luchevoy terapii i luchevoy diagnostiki (Pre-irradiation preparation using three dimensional planning. : Quality control in radiotherapy and radiologic diagnosis). Minsk, 2009: 261–70.]
  13. ICRU Report 50: Prescribing, Recording and Reporting Photon Beam Therapy. Bethesda: International Commission on Radiation Units and Measurements, 1993.
  14. ICRU Report 62: Prescribing, Recording and Reporting Photon Beam Therapy. Bethesda: International Commission on Radiation Units and Measurements, 1999.
  15. Leeuwen F.E., Klokman W.J., Stovall M. Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin’s disease. J. Natl. Cancer Inst. 2003; 95(13): 971–80.
  16. Markova J., Kobe С., Skopalova М. FDG–PET for assessment of early treatment response after four cycles of chemotherapy in patients with advancedstage Hodgkin’s lymphoma has a high negative predictive value. Ann. Oncol. 2009; 20(7): 1270–4.

 

Основные закономерности ангиогенеза при онкогематологических заболеваниях

ОБЗОРЫ , , ,

А.А. Вартанян

ФГБУ «Российский онкологический центр им Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Концепция о том, что VEGF-индуцируемый ангиогенез — фактор, лимитирующий рост солидных опухолей, сегодня считается общепринятой. Исследования последних лет показывают, что ангиогенез также необходимое условие прогрессии онкогематологических заболеваний. Процесс ветвления близлежащих сосудов в костном мозге начинается с выброса опухолевыми клетками растворимых активаторов ангиогенеза. Основным медиатором, стимулирующим формирование микрососудов в костном мозге, считается VEGF. С другой стороны, повышенная секреция VEGF приводит к высвобождению клетками микроокружения GM-CSF, G-CSF, IL-6, PlGF, HGF, IGF, цитокинов, способствующих выживанию и пролиферации злокачественных миелоидных и лимфоидных клеток. Увеличение уровня VEGF в плазме онкогематологических больных считается неблагоприятным прогностическим фактором течения болезни.

В настоящем обзоре обсуждаются основные закономерности формирования аутокринного и паракринного пула VЕGF, ангиогенез-зависимая и -независимая функции VEGF, а также результаты клинического изучения антиангиогенных препаратов в онкогематологии.

Ключевые слова: онкогематология, костный мозг, ангиогенез, антиангиогенная терапия.

Читать статью в PDFpdficon

Литература 

  1. Folkman J. Fundamental concepts of the angiogenic process. Curr. Mol. Med. 2003; 3: 643–51.
  2. Bouck N., Stellmach V., Hsu S.C. How tumors become angiogenic. Adv. Cancer Res. 1996; 69: 135–74.
  3. Eiken H.M., Adams R.M. Dynamics of endothelial cell behaviour in sprouting angiogenesis. Curr. Opin. Cell Biol. 2010; 22(5): 617–25.
  4. Feige J.J. Tumour angiogenesis: recent progress and remaining challenges. Bull. Cancer 2010; 97(11): 1305–10.
  5. Tischer E., Mitchell R., Hartman T. et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J. Biol. Chem. 1991; 266(18): 11947–54.
  6. Shibuya M. Differential roles of vascular endothelial growth factor receptor-1 and receptor-2 in angiogenesis. J. Biochem. Mol. Biol. 2006; 39: 469–78.
  7. Hauser S., Weich H.A. A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein EC and in placenta. Growth Factors 1993; 9(4): 259–68.
  8. Straume O., Akslen L.A. Importance of vascular phenotype by basic fibroblast growth factor, and influence of the angiogenic factors basic fibroblast growth factor/fibroblast growth factor receptor-1 and Ephrin-A1/EphA2 on melanoma progression. Am. J. Pathol. 2002; 160: 1009–19.
  9. Maisonpierre P.C., Suri C., Jones P.F. et al. Angiopoietin-2, a natural antagonist for Tie-2 that disrupts in vivo angiogenesis. Science (London) 1997; 277: 55–60.
  10. Sharma P.S., Sharma R., Tyagi T. VEGF/VEGFR pathway inhibitors as anti-angiogenic agents: Present and Future. Curr. Cancer Drug Targets 2011; 11(5): 624–33.
  11. Fliedner T.M., Feinendegen L.E., Hopewell J.W. et al. Chronic irradiation: tolerance and failure in complex biological system. Br. J. Radiol. 2002; Supp. 126: 21–6.
  12. Podar K., Andersen K. Emerging therapies targeting tumor vasculature in multiple myeloma and other haematological malignancies. Curr. Cancer Drug Targets 2011; 11(9): 1005–24.
  13. Bradford G.B., Williams B., Rossi R. et al. Quiescence, cycling and turnover in the hematopoietic stem cell compartment. Exp. Hematol. 1997; 25(5): 445–53.
  14. Cuiffo B.G., Karnoub A.E. Mesenchimal stem cells in tumor development: emerging roles and concepts. Cell Adh. Migr. 2012; 6(3): 220–30.
  15. Schofield R. The relationship between the spleen colony-forming cell and the hematopoietic stem cell: A hypothesis. Blood Cells 1978; 4(1–2): 7–25.
  16. Vila L., Thomas X., Campos L. et al. Expression of VLA molecules on acute leukemia cells: relationship with disease characteristics. Exp. Hematol. 1995; 23: 514–8.
  17. Gong J.K. Endosteal marrow: a rich source of hematopoietic stem cells. Science 1978; 199: 1443–5.
  18. Taichman R.S., Reil W.J., Emerson S.G. Human osteoblasts support human hematopoietic progenitor stem cell in vitro bone marrow cultures. Blood 1996; 87: 518–24.
  19. Calvi L.M., Adams G.B., Weibrecht K.W. et al. Osteoblast cells regulate the hematopoietic stem cell niche. Nature 2003; 425: 841–6.
  20. Zhang J., Niu C., Ye L. et al. Identification of the hematopoietic stem cell niches and control of the niche size. Nature 2003; 425: 836–41.
  21. Yin T., Li L. The stem cell niches in bone. J. Clin. Invest. 2006; 116(5): 1195–201.
  22. Doan P.L., Chute J.P. The vascular niche: home for normal and malignant hematopoietic stem cells. Leukemia 2012; 26: 54–62.
  23. Raffi S., Shapiro F., Pettengell R. et al. Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors. Blood 1995; 86: 3753–63.
  24. Davis T.A., Robinson D.N., Lee K.P. et al. Porcine microvascular endothelial cells support the in vitro expansion of the human primitive hematopoietic bone marrow progenitor cells with a high replanting potential: requirement for cell-to-cell interaction and colony-stimulating factors. Blood 1995; 85: 1751–61.
  25. Chute J.P., Muramoto G.G., Fung J. et al. Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34+CD38-cells and SCID-repopulating cells. Blood 2005; 105: 576–83.
  26. Kaplan R.N., Psaila B., Lyden C. Niche-to-niche migration of bone marrow-derived cells. Trends Mol. Med. 2007; 13(2): 72–81.
  27. Gerber H.P., Ferrara N. The role of VEGF in normal and neoplastic hematopoiesis. J. Mol. Med. (Berlin) 2003; 81: 20–31.
  28. Grandage V.L., Gale R.E., Linch D.C. et al. PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, MAPK and p53 pathways. Leukemia 2005; 19: 586–94.
  29. Lewis T.S., Shapiro P.S., Ahn N.G. Signal transduction through MAP kinase cascades. Adv. Cancer Res. 1998; 74: 49–139.
  30. Weber-Nordt R.M., Mertelsmann R., Finke J. The JAK-STAT pathway: signal transduction involved in proliferation, differentiation and transformation. Leuk. Lymphoma 1998; 28: 459–67.
  31. Dias S., Hattori K., Zhu Z. et al. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J. Clin. Invest. 2000; 106: 511–21.
  32. Glenjen N.I., Hatfield K., Bruserud O. et al. Coculture of native human acute myelogenous leukemia blasts with fibroblasts and osteoblasts results in an increase of vascular endothelial growth factor levels. Eur. J. Haematol. 2005; 74: 24–34.
  33. Podar K., Anderson K.C. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood 2005; 105: 1383–95.
  34. Paesler J., Gehrke I., Poll-Wolbeck S.J., Kreuzer K.A. Targeting the vascular endothelial growth factor in hematologic malignancies. Eur. J. Hematol. 2012; 89: 373–84.
  35. Wegiel B., Ekberg J., Talasila K.M. et al. The role of VEGF and a functional link between VEGF and p27Kip1 in acute myeloid leukemia. Leukemia 2009; 23: 251–61.
  36. Ramakrishnan V., Timm M., Haug J.L. et al. Sorafenib, a dual Raf kinase/ vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs. Oncogene 2010; 29: 1190–202.
  37. Podar K., Catley L.P., Tai Y.T. et al. GW654652, the paninhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment. Blood 2004; 103: 3474–9.
  38. Kovacs M.J., Reece D.E., Marcellus D. et al. A phase II study of ZD6474 (Zactima, a selective inhibitor of VEGFR and EGFR tyrosine kinase) in patients with relapsed multiple myeloma–NCIC CTG IND. Invest. New Drugs 2006; 24: 529–35.
  39. Karp J.E., Gojo I., Pili R. et al. Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-darabinofuranosylcytosine, mitoxantrone, and bevacizumab. Clin. Cancer Res. 2004; 10: 3577–85.
  40. Barbarroja N., Torres L.A., Luque M.J. et al. Additive effect of PTK787/ ZK 222584, a potent inhibitor of VEGFR phosphorylation, with Idarubicin in the treatment of acute myeloid leukemia. Exp. Hematol. 2009; 37: 679–91.
  41. Smolich B.D., Yuen H.A., West K.A. et al. The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood 2001; 97: 1413–21.
  42. Paesler J., Gehrke I., Gandhirajan R.K. et al. The vascular endothelial growth factor receptor tyrosine kinase inhibitors vatalanib and pazopanib potently induce apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Clin. Cancer Res. 2010; 16: 3390–8.
  43. Huber S., Oelsner M., Decker T. et al. Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1. Leukemia 2011; 25: 838–47.
  44. Shanafelt T., Zent C., Byrd J. et al. Phase II trials of single agent anti-VEGF therapy for patients with chronic lymphocytic leukemia. Leuk. Lymphoma 2010; 51: 2222–9.
  45. Lee Y.K., Shanafelt T.D., Bone N.D. et al. VEGF receptors on chronic lymphocytic leukemia (CLL) B cells interact with STAT 1 and 3: implication for apoptosis resistance. Leukemia 2005; 19: 513–23.
  46. Li F.F., Zheng G.H., Xu Y.H. et al. Effect of siRNA targeting VEGF on cell apoptosis and the expression of surviving in K562 cells. Zhonghua Xue Ye Xue Za Zhi. 2009; 30: 825–8.
  47. Reiners K.S., Gossmann A., von Strandmann E.P. et al. Effects of the antiVEGF monoclonal antibody bevacizumab in a preclinical model and in patients with refractory and multiple relapsed Hodgkin lymphoma. J. Immunother. 2009; 32: 508–12.
  48. Moehler T.M., Ho A.D., Goldschmidt H. et al. Angiogenesis in hematologic malignancies. Crit. Rev. Oncol. Hematol. 2003; 45: 227–44.
  49. Aguayo A., Kantarjian H., Manshouri T. et al. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 2000; 96: 2240–5.
  50. Flater J.L., Kay M.E., Goolsby C.L. et al. Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical and cytometric evidence. Diagn. Pathol. 2008; 3: 1–16.
  51. Lee C.Y., Tien H.F., Hu C.Y. et al. Marrow angiogenesis-associated factors as prognosric biomarkers in patients with acute myelogenous leukemia. Br. J. Cancer 2007; 97(7): 877–82.
  52. Lin N.I., Lin D.T., Chang C.J. et al. Marrow matrix metalloptoteinases (MMPs) and tissue inhibitor of MMP in acute leukemia: potential role of MMP-9 as surrogate marker to monitor leukemic status in patients with acute myelogenous leukemia. Br. J. Leuk. 2002; 117: 835–41.
  53. Hattori K., Heissig B., Wu Y. et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat. Med. 2002; 8: 841–9.
  54. Fragoso R., Pereira T., Wu Y. et al. VEGFR-1 (FLT-1) activation modulates acute lymphoblastic leukemia localization and survival within the bone marrow, determining the onset of extramedullary disease. Blood 2006; 107: 1608–16.
  55. Van de Veire S., Stalmans I., Heindryckx F. et al. Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell 2010; 141: 178–90.
  56. Schmidt T., Kharabi Masouleh B., Loges S. et al. Loss or inhibition of stromal-derived PlGF prolongs survival of mice with imatinib-resistant Bcr-Abl1+ leukemia. Cancer Cell 2011; 19(6): 740–53.
  57. Yetgin S., Yenicesu I., Cetin M. et al. Clinical importance of serum vascular endothelial and basic fibroblast growth factors in children with acute lymphoblastic leukemia. Leuk. Lymphoma 2001; 42(1–2): 83–8.
  58. De Raeve H., Van Mark E., Van Camp B. et al. Angiogenesis and the role of bone marrow endothelial cells in hematologic malignancies. Histol. Histopathol. 2004; 19: 935–50.
  59. Arai H., Hirao A., Suda T. Regulation of hematopoietic stem cells by the niche. Trends Cardiovasc. Med. 2005; 15: 75–9.
  60. Rabitsch W., Sperr W.R., Lechner K. et al. Bone marrow microvessel density and its prognostic significance in AML. Leuk. Lymphoma 2004; 45(7): 1369–73.
  61. Pule M.A., Gulmann C., Derris D. et al. Increased angiogenesis in bone marrow of children with acute lymphoblastic leukemia has no prognostic significance. Br. J. Haematol. 2002; 118(4): 991–8.
  62. Kasparova P., Smolei L. Angiogenesis in the bone marrow of patients with chronic lymphocytic leukemia. Cesk. Patol. 2007; 43(2): 50–8.
  63. Zhelvazkova A.G., Tochev A.B., Kolova P. et al. Prognostic significance of hepatocyte growth factor and microvessel bone marrow density in patients with chronic myeloid leukemia. Scand. J. Clin. Lab. Invest. 2008; 68(6): 492–500.
  64. Zhao S., Zhang Q.Y., Ma W.J. et al. Analysis of 31 cases of primary breast lymphoma: the effect of nodal involvement and microvascular density. Clin. Lymphoma Myeloma Leuk. 2011; 11(1): 33–7.
  65. De Raeve H., Van Marck E., Van Camp B. et al. Angiogenesis and the role of bone marrow endothelial cells in haematological malignancies. Histol. Histopathol. 2004; 19(3): 935–50.
  66. Kvasnicka H.M., Thiele J. Bone marrow angiogenesis: methods of quantification and changes evolving in chronic myeloproliferative disorders. Histol. Histopathol. 2004; 19(4): 1245–60.
  67. Shih T.T., Hou H.A., Liu C.Y. et al. Bone marrow angiogenesis magnetic resonance imaging in patients with acute myeloid leukemia: peak enhancement ratio is an independent predictor for overall survival. Blood 2009; 113(14): 3161–7.
  68. Chen B.-B., Hsu C.-Y., Yu C.-W. et al. Dynamic contrast-enhanced MR imaging measurement of vertebral bone marrow perfusion may be indicator of outcome of acute leukemia patients in remission. Radiology 2011; 258(3): 821–31.
  69. Singhal S., Mehta J., Desikan R. et al. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med. 1999; 341(21): 1565–71.
  70. Rehman W., Arfons L.M., Lazarus H.M. The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development. Ther. Adv. Hematol. 2011; 2(5): 291–308.
  71. Maiolino A., Hungria V.T., Garnica M. et al. Multiple Myeloma Study Group (BMMSG/GEMOH). Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progressionfree survival in multiple myeloma. Am. J. Hematol. 2012; 87(10): 948–52.
  72. Sher T., Ailawadhi S., Miller K.C. et al. A steroid-independent regimen of bortezomib, liposomal doxorubicin and thalidomide demonstrate high response rates in newly diagnosed multiple myeloma patients. Br. J. Haematol. 2011; 154(1): 104–10.
  73. Fayers P.M., Palumbo A., Hulin C. et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patients from 6 randomized clinical trials. Blood 2011; 118: 1239–47.
  74. Kotla V., Goel S., Nischal S. et al. Mechanism of action of thalidomide in hematological malignancies. J. Hematol. Oncol. 2009; 2: 36–46.
  75. Li S., Gill N., Lentzsch S. Recent advances of IMiDs in cancer therapy. Curr. Opin. Oncol. 2010; 22(6): 579–85.
  76. Shortt J., Hsu A.K., Johnstone R.W. Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy. Oncogene 2013; 32(1): 1–18.
  77. Wang M., Dimopoulos M.A., Chen C. et al. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood 2008; 112(12): 4445–51.
  78. Dimopoulos M.A., Kastritis E., Christoulas D. et al. Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenic abnormalities and of previous therapies. Leukemia 2010; 24 (10): 1769–78.
  79. Williams S., Pettaway C., Song R. et al. Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts. Mol. Cancer Ther. 2003; 2(9): 835–43.
  80. Chen Y., Borthakur G. Lenalidomide as a novel treatment of acute myeloid leukemia. Exp. Opin. Invest. Drugs 2013; 22(3): 389–97.
  81. Wiernik P.H. Lenalidomide in lymphomas and chronic lymphocytic leukemia. Exp. Opin. Pharmacother. 2013; 14(4): 475–88.
  82. Blum W., Klisovic R.B., Becker H. et al. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J. Clin. Oncol. 2010; 28: 4919–25.
  83. Tageja N. Lenalidomide — current understanding of mechanistic properties. Anticancer Agents Med. Chem. 2011; 11(3): 315–26.
  84. Davies F., Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev. 2010; Suppl. 1: S13–9.
  85. San-Miguel J.F. Long-term disease control in multiple myeloma: the impact of the dual mechanism of action of lenalidomide. Introduction and overview. Blood Rev. 2010; Suppl. 1: S1–3.
  86. Li Z.W., Chen H., Campbell R.A. et al. NF-kappaB in the pathogenesis and treatment of multiple myeloma. Curr. Opin. Hematol. 2008; 15(4): 391–9.
  87. Bartlett J.B., Tozer A., Stirling D. et al. Recent clinical studies of the immunomodulatory drug (IMiD) lenalidomide. Br. J. Cancer 2005; 93(6): 613–9.
  88. Ribatti D., Mangialaedi G., Vacca A. Antiangiogenic therapeutic approaches in multiple myeloma. Curr. Cancer Drug Targets 2012; 12: 768–75.
  89. Lin B., Podar K., Gupta D. et al. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment. Cancer Res. 2002; 62(17): 5019–26.
  90. Zangari M., Anaissie E., Stopeck A. et al. Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma. Clin. Cancer Res. 2004; 10(1 Pt. 1): 88–9.
  91. Podar K., Catley L.P., Tai Y.T. et al. GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment. Blood 2004; 103 (9): 3474–9.
  92. Ramakrishnan V., Timm M., Haug J.L. et al. Sorafenib, a dual Raf kinase/vascular endothelial growth factor receptor inhibitor has significant antimyeloma activity and synergizes with common anti-myeloma drugs. Oncogene 2010; 29(8): 1190–202.
  93. Breccia M., Salaroli A., Molica M. et al. Systematic review of dasatinib in chronic myeloid leukemia. Oncol. Targets Ther. 2013; 6: 257–65.
  94. Wiernik P.H. FLT3 inhibitors for the treatment of acute myeloid leukemia. Clin. Adv. Hematol. Oncol. 2010; 8(6): 429–36.
  95. Roboz G.J., Giles F.J., List A.F. et al. Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. Leukemia 2006; 20(6): 952–7.
  96. Macdonald D.A., Assouline S.E., Brandwein J. et al. A phase I/II study of sorafenib in combination with low dose cytarabine in elderly patients with acute myeloid leukemia or high-risk myelodysplastic syndrome from the National Cancer Institute of Canada Clinical Trials Group: trial IND.186. Leuk. Lymphoma 2013; 54(4): 760–6.
  97. Nishioka C., Ikezoe T., Yang J. et al. Sunitinib, an orally available receptor tyrosine kinase inhibitor, induces monocytic differentiation of acute myelogenous leukemia cells that is enhanced by 1,25-dihydroxyvitamin D(3). Leukemia 2009; 23(11): 2171–3.
  98. Stopeck A., Sheldon M., Vanedian M. et al. Results of a Phase I Dose-escalating Study of the Antiangiogenic Agent, SU5416, in Patients with Advanced Malignancies. Clin. Cancer Res. 2002; 8: 2798–3011.
  99. Fiedler W., Mesters R., Heuser M. et al. An open-label, Phase I study of cediranib (RECENTIN) in patients with acute myeloid leukemia. Leuk. Res. 2010; 34(2): 196–202.
  100. Thomas X. Acute lymphoblastic leukemia with Philadelphia chromosome: treatment with kinase inhibitors. Bull. Cancer 2007; 94(10): 871–80.
  101. Mirshahi P., Raffi A., Vincent I. et al. Vasculogenic mimicry of acute leukemic bone marrow stromal cells. Leukemia 2009; 23: 1039–48.
  102. Scavelli C., Nico B., Cirulli T. et al. Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma. Oncogene 2008; 27(5): 663–74.
  103. Nico B., Margieri D., Crivellato E. et al. Mast cells contribute to vasculogenic mimicry in multiple myeloma. Stem Cell Dev. 2008; 17(1): 19–22.

 

Множественная миелома (патогенез, клиника, диагностика, дифференциальный диагноз). Часть I

ОБЗОРЫ , , , ,

С.С. Бессмельцев

Российский научно-исследовательский институт гематологии и трансфузиологии, Санкт-Петербург, Российская Федерация

РЕФЕРАТ

Множественная миелома (ММ) — опухолевое заболевание, характеризующееся инфильтрацией костного мозга плазматическими клетками и обширным поражением костей скелета, что сопровождается болью и переломами костей. В обзоре представлены лабораторные признаки и клинические симптомы, характерные для ММ. Диагноз ММ не вызывает сомнений при обнаружении в костном мозге больных 10 % и более клональных плазматических клеток, M-протеина в сыворотке или моче (кроме несекретирующей миеломы), гиперкальциемии, почечной недостаточности, анемии или очагов лизиса в костях скелета. Для выявления М-протеина используют электрофорез сывороточных белков и иммунофиксацию. Кроме того, необходимы электрофорез и иммунофиксация мочевых белков или определение свободных легких цепей иммуноглобулинов. Международная система стадирования в зависимости от уровня b2-микроглобулина и альбумина в сыворотке подразделяет больных ММ на три группы риска: стандартного, промежуточного и высокого. Анализ хромосомных нарушений позволяет более надежно стратифицировать больных на группы риска. Установлено, что del(13), t(4;14) или t(14;16), del(17p), гиподиплоидия и индекс метки плазматических клеток 3 % и более существенно ухудшают прогноз ММ.

В обзоре представлены лабораторные признаки и клинические симптомы моноклональной гаммапатии неясного генеза/неопределенного значения, асимптоматической миеломы (тлеющей миеломы), несекретирующей миеломы, солитарной плазмоцитомы кости, экстрамедуллярной плазмоцитомы, плазмоклеточного лейкоза, макроглобулинемии Вальденстрема, амилоидоза и других заболеваний.

Ключевые слова: множественная миелома, моноклональные гаммапатии неясного генеза, асимптоматическая миелома, M-протеин, клональные плазматические клетки.

Читать статью в PDFpdficon

ЛИТЕРАТУРА

  1. Harousseau J.-L., Dreyling M., on behalf of the ESMO Guidelines Working Group. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Oncology 2010; 21(Suppl. 5): v155–7.
  2. Бессмельцев С.С., Абдукадыров К.М. Множественная миелома. Современный взгляд на проблему. Алматы, 2007. [Bessmeltsev S.S., Abdukadyrov K.M. Mnozhestvennaya miyeloma. Sovremennyy vzglyad na problemu (Multiple myeloma. Current view of the problem). Almaty, 2007.]
  3. Kyle R.A., Rajkumar S.V. Multiple myeloma. Engl. J. Med. 2004; 351(18): 1860–73.
  4. Fonseca R., Bergsagel P.L., Drach J. et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009; 23(12): 2210–21.
  5. Anderson K.C. Targeted therapy for multiple myeloma. Hematol. 2001; 38: 286–94.
  6. Barker H.F., Ball J., Drew M. et al. The role of adhesion molecules in multiple myeloma. Lymphoma 1992; 8: 189–96.
  7. Харченко М.Ф., Бессмельцев С.С. Значение протеогликанов в патоге- незе множественной миеломы. Биомед. журн. Medline.ru. 2010; 11: 404–23. [Kharchenko M.F., Bessmeltsev S.S. Znacheniye proteoglikanov v patogeneze mnozhestvennoy miyelomy (Significance of proteoglycans in pathogenesis of multiple myeloma. In: Biomed. journ.). Biomed. zhurn. Medline.ru. 2010; 11: 404–23.]
  8. Stringer S.E. The role of heparan sulfate proteoglycans in angiogenesis. Soc. Trans. 2006; 34: 451–3.
  9. Andersen N., Standal T., Nielsen J. et al. Syndecan-1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival. J. Haemat. 2004; 128: 210–7.
  10. Klein B., Tarte K., Jourdan M. et al. Survival and proliferation factors of normal and malignant plasma cells. J. Hematol. 2003; 78: 106–13.
  11. Mahtouk K., Cremer F., Reme T. et al. Heparan sulfate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma. Oncogene 2006; 25: 7180–91.
  12. Purushothaman A., Uyama T., Kobayashi F. Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis. Blood 2010; 115: 2449–57.
  13. Damiano J.S., Gress A.E., Hazlehurst L.A. et al. Cell adhesion mediated drug resistance: Role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 1999; 93: 1658–67.
  14. Damiano J.S., Dalton W.S. Integrin-mediated drug resistance in multiple myeloma. Lymphoma 2000; 38: 71–81.
  15. Shain K., Landowski T., Dalton W.S. Cellular adhesion via Beta 1 integrins increases c-FLIPL levels and inhibits CD95/Fas-mediated apoptosis in hematologic malignancies: A mechanism of immune evasion. 2001.
  16. Davies F.E., Anderson K.C. Novel therapeutic targets in multiple myeloma. J. Hematol. 2000; 64: 359–67.
  17. Anderson K.C. Targeted therapy for multiple myeloma. Hematol. 2001; 38: 286–94.
  18. Klein B., Zhang X., Lu Z. Interleukin-6 in multiple myeloma. Blood 1995; 85: 863–7.
  19. Karin M., Cao Y., Greten F.R., Li Z.W. NF-kappaB in cancer: from innocent bystander to major culprit. Rev. Cancer 2002; 2: 301–10.
  20. Barlogie B., Epstein J., Selvanayagam P., Alexanian R. Plasma cell myeloma — new biological insights and advances in therapy. Blood 1998; 73: 865–70.
  21. Fonseca R., Oken M.H., Harrington D. et al. deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia 2001; 15: 981–6.
  22. Fonseca R., Debes-Marun C.S., Picken E.B. et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood 2003; 102(7): 2562–7.
  23. Mohamed A.N., Bentley G., Bonnett M.L. et al. Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes. J. Hematol. 2007; 82: 1080–7.
  24. Chesi M., Nardini E., Lim R.C. et al. The t(4;14) translocation in multiple myeloma disregulates both FGFR 3 and novel gene, MMSET, resulting in IgH/ MMSET hybrid transcripts. Blood 1998; 92: 3025–34.
  25. Avet-Loiseau H., Attal M., Campion L. et al. Long-term analysis of the IFM 99 trials for myeloma: Cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. Clin. Oncol. 2012; 30: 1949–52.
  26. Avet-Loiseau H., Minvielle S., Mellerin M.P. et al. 14q32 chromosomal translocations: A hallmark of plasma cell dyscrasias? J. 2000; 1: 292–4.
  27. Fonseca R., Debes-Marun C.S., Picken E.B. et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood 2003; 102(7): 2562–7.
  28. Avet-Loiseau H., Facon T., Daviet A. et al. 14q32 translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma. Intergroupe Francophone du Myelome. Cancer Res. 1999; 59: 4546–50.
  29. Shaughnessy J.Jr., Cabren A.Q. Cyclin D3 at 6h21 is deregulated by recurrent chromosome translocation to immunoglobulin loci in multiple myeloma. Blood 2001; 98: 217–23.
  30. Santra M., Zhan F., Tian E. et al. A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript. Blood 2003; 101: 2374–6.
  31. Broyl A., Hose D., Lokhorst H. et al. Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood 2010; 116: 2543–6.
  32. Sawyer J.R., Lukacs J.L., Thomas E.L. et al. Multicolour spectral karyotyping identifies new translocation and a recurring pathway for chromosome loss in multiple myeloma. J. Haematol. 2000; 112: 1–9.
  33. Bednarek A.K., Keck-Waggoner C.L., Daniel R.L. et al. WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res. 2001; 61: 8068–73.
  34. Shou Y., Martelli M.L., Gabrea A. et al. Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma. Natl. Acad. Sci. USA 2000; 97: 228–33.
  35. Shaughnessy J.Jr., Tian E., Sawyer J. et al. High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH. Blood 2000; 96: 1505–11.
  36. Fonseca R., Oken M.H., Harrington D. et al. deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy. Leukemia 2001; 15: 981–6.
  37. Boersma-Vreugdenhill G.R., Kuipers J., Bast B.J. Breakpoint analysis of a novel recurrent chromosomal translocation t(14;20)(q32;q12) in a human multiple myeloma cell line. VIIIth International Myeloma Workshop. Banff, Alberta, Canada, 2001: 124.
  38. Fonseca R., Bergsagel P.L., Drach J. et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia 2009; 23: 2210–21.
  39. Walker B.A., Leone P.E., Chiecchio L. et al. A compendium of myelomaassociated chromosomal copy number abnormalities and their prognostic value. Blood 2010; 116: e56–65.
  40. Hanamura I., Stewart J.P., Huang Y. et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood 2006; 108: 1724–32.
  41. Liu P.C., Leong T., Quam L. et al. Activating mutations of N- and K-ras in multiple myeloma show different clinical associations — analysis of the Eastern Cooperative Oncology Group phase III trial. Blood 1996; 88: 2699–706.
  42. Urashima M., Teoh G., Ogata A. et al. Characterization of p16(INK4A) expression in multiple myeloma and plasma cell leukemia. Cancer Res. 1997; 3: 2173–9.
  43. Dimopoulos M., Kyle R., Fermand J.-P. et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus. Panel 3. Blood 2011; 117(18): 4701–5.
  44. Baur-Melnyk A., Buhmann S., Durr H.R., Reiser M. Role of MRI for the diagnosis and prognosis of multiple myeloma. J. Radiol. 2005; 55(1): 56–63.
  45. Moulopoulos L.A., Gika D., Anagnostopoulos A. et al. Prognostic significance of magnetic resonance imaging of bone marrow in previously untreated patients with multiple myeloma. Oncol. 2005; 16(11): 1824–8.
  46. Walker R., Barlogie B., Haessler J. et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. Clin. Oncol. 2007; 25(9): 1121–8.
  47. Durie B.G., Waxman A.D., D’Angolo A., Williams C.M. Whole-body FDG PET identifies high-risk myeloma. Nucl. Med. 2002; 43(11): 1457–63.
  48. Sezer O. Myeloma bone disease. Hematology 2005; 10(Suppl. 1): 19–24.
  49. Piarse R.N., Sordillo E.M., Yaccoby S. et al. Multiple myeloma disrupts the TRANCE/osteoprotegerin cytocine axons to trigger bone destruction and promote tumor progression. Natl. Acad. Sci. USA 2001; 98: 11581–6.
  50. Heider U., Langelotz C., Jakob C. et al. Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma. Cancer Res. 2003; 9: 1436–40.
  51. Seidel C., Hirtner O., Abildgaard N. et al. Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease. Blood 2001; 98: 2269–71.
  52. Abe M., Hiura K., Wilde J. et al. Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma. Blood 2002; 100: 2195–202.
  53. Zannettino A.C., Farrugia A.N., Kortesidis A. et al. Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients. Cancer Res. 2005; 65: 1700–9.
  54. Tian E., Zhan F., Walker R. et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. Engl. J. Med. 2003; 349: 2483–6.
  55. Бессмельцев С.С., Карягина Е.В., Стельмашенко Л.В. и др. Частота, характеристика и методы лечения периферической нейропатии у больных множественной миеломой, получающих бортезомиб (велкейд). Онкогема- тология 2008; 3: 52–62. [Bessmeltsev S.S., Karyagina Ye.V., Stelmashenko L.V. i dr. Chastota, kharakteristika i metody lecheniya perifericheskoy neyropatii u bolnykh mnozhestvennoy miyelomoy, poluchayushchikh bortezomib (velkeyd) (Incidence, characteristics, and methods of therapy for peripheral neuropathy in patients with multiple myeloma treated with bortezomib (Velcade). In: Oncohematology). Onkogematologiya 2008; 3: 52–62.]
  56. Rajkumar S.V., Fonseca R., Dispenzieri A. et al. Methods for estimation of bone marrow plasma cell involvement in myeloma: predictive value for response and survival in patients undergoing autologous stem cell transplantation. J. Hematol. 2001; 68(4): 269–75.
  57. Ругаль В.И., Бессмельцев С.С. Оценка опухолевой инфильтрации костного мозга при множественной миеломе по результатам исследования трепанобиоптатов. Вестн. гематол. 2009; 5(1): 49–50. [Rugal V.I., Bessmeltsev S.S. Otsenka opukholevoy infiltratsii kostnogo mozga pri mnozhestvennoy miyelome po rezultatam issledovaniya trepanobioptatov (Assessment of bone marrow tumor infiltration based on trephine biopsy findings. In: Hematol. bullet.). Vestn. gematol. 2009; 5(1): 49–50.]
  58. Людвиг Х., Остерборг А. Анемия и терапия эритропоэтином при множе- ственной миеломе. Анемия у онкологических больных. 2002; 1(Вып. 1): 3–10. [Lyudvig Kh., Osterborg A. Anemiya i terapiya eritropoetinom pri mnozhestvennoy miyelome (Anemia and erythropoietin therapy in multiple myeloma. In: Anemia in cancer patients). Anemiya u onkologicheskikh bolnykh. 2002; 1(Vyp. 1): 3–10.]
  59. Бессмельцев С.С., Гусева С.А. Современные принципы лечения анемии у пациентов с онкогематологическими заболеваниями. Украiн. журн. гематол. та трансфузiол. 2009; 1: 5–17. [Bessmeltsev S.S., Guseva S.A. Sovremennye printsipy lecheniya anemii u patsientov s onkogematologicheskimi zabolevaniyami (Current principles of therapy for anemia in patients with hematological malignancies. In: Ukraine journal of hematol. & transfusiol.). Ukrain. zhurn. gematol. ta transfuziol. 2009; 1: 5–17.]
  60. Abdulkadyrov K.M., Bessmeltsev S.S. Renal insufficiency in multiple myeloma: Basic mechanisms in its development and methods for treatment. Renal Fail. 1996; 18(1): 139–46.
  61. Faiman B.M., Spong J., Tariman J.D. Renal Complications in Multiple Myeloma and Related Disorders: Survivorship Care Plan of the International Myeloma Foundation Nurse Leadership Board. J. Oncol. Nurs. 2011; 15(4): 66–76.
  62. Бессмельцев С.С. Бисфосфонаты и их роль в лечении множественной миеломы. Украiн. журн. гематол. та трансфузiол. 2011; 1: 5–18. [Bessmeltsev S.S. Bisfosfonaty i ikh rol v lechenii mnozhestvennoy miyelomy (Bisphosphonates and their role in therapy for multiple myeloma. In: Ukraine journ. of hematol. & transfusiol.). Ukrain. zhurn. gematol. ta transfuziol. 2011; 1: 5–18.]
  63. Чубукина Ж.В., Бубнова Л.Н., Бессмельцев С.С. и др. Неспецифические факторы защиты и гуморальный иммунитет у больных множественной миеломой. Мед. экстрем. ситуаций 2012; 2: 93–8. [Chubukina Zh.V., Bubnova L.N., Bessmeltsev S.S. i dr. Nespetsificheskiye faktory zashchity i gumoralnyy immunitet u bolnykh mnozhestvennoy miyelomoy (Non-specific protective factors and humoral immunity in patients with multiple myeloma. In: Med. of extr. situations). Med. ekstrem. situatsiy 2012; 2: 93–8.]
  64. Бессмельцев С.С., Стельмашено Л.В., Степанова Н.В. и др. Бортезомиб (велкейд) и мелфалан с преднизолоном в лечении множественной миеломы у пожилых больных. Онкогематология 2010; 2: 40–5. [Bessmeltsev S.S., Stelmasheno L.V., Stepanova N.V. i dr. Bortezomib (velkeyd) i melfalan s prednizolonom v lechenii mnozhestvennoy miyelomy u pozhilykh bolnykh (Bortezomib (Velcade) and melphalan combined with prednisolone in therapy for multiple myeloma in older patients. In: Oncohematology). Onkogematologiya 2010; 2: 40–5.]
  65. Noel C., Ales D.O., Jasmine T. et al. Multiple Myeloma-Associated Amyloidosis Manifesting as Fulminant Hepatic Failure. South Med. J. 2001; 94(10) http://www.medscape.com/viewarticle/415092_5
  66. Dispenzieri A., Kyle R., Merlini G. et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23(2): 215–24.
  67. Blade J., Lust J.A., Kyle R.A. Immunoglobulin D multiple myeloma: presenting features, response to therapy, and survival in a series of 53 cases. Clin. Oncol. 1994; 12: 2398–404.
  68. Reece D.E., Vesole D.H. Outcome of Patients With IgD and IgM Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Retrospective CIBMTR Study Clinical Lymphoma. Leuk. 2010; 10(6): 458–63.
  69. Avet-Loiseau H., Garand R., Lode L. et al. Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants. Blood 2003; 101: 1570–1.
  70. Durie B.G.M., Salmon S.E. A clinical staging system for multiple myeloma: Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975; 36: 842–54.
  71. Greipp P.R., San Miguel J., Durie B.G.M. et al. International Staging System for Multiple Myeloma. Clin. Oncol. 2005; 23: 3412–20.
  72. Tuchman S.A., Sagar Lonial. High-Risk Multiple Myeloma: Does it Still Exist? Lymph. Myel. Leuk. 2011; 11(1): S70–6.
  73. Kyle R.A., Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23: 3–9.
  74. Hari P.N., Zhang M.J., Roy V. et al. Is the international staging system superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous transplant. Leukemia 2009; 23: 1528–34.
  75. Avet-Loiseau H., Attal M., Moreau P. et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood 2007; 109: 3489–95.
  76. Dimopoulos M.A., Kastritis E., Christoulas D. et al. Treatment of patients with relapsed/refractory multiple myeloma (MM) with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities. Blood (ASH Annual Meeting Abstracts) 2009; 114: Abstract 958.
  77. Sawyer J., Shaughnessy J.D., Haussler J. et al. Gene expression profiling (GEP) in multiple myeloma (MM): Distinguishing relapses with high-risk transformation from those with sustained low risk. Clin. Oncol. 2010; 28: 15s (suppl; abstr. 8122).
  78. Kumar S.K., Mikhael J.R. Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines. Mayo Clin. Proc. 2009; 84(12): 1095–110.
  79. Fonseca R., Blood E., Rue M. et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101(11): 4569–75.
  80. Gertz M.A., Lacy M.Q., Dispenzieri A. et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005; 106(8): 2837–40.
  81. Dispenzieri A., Rajkumar S.V., Gertz M.A. et al. Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-Adapted therapy (mSMART). Mayo Clin. Proc. 2007; 82: 323–41.
  82. Бессмельцев С.С. Диагностика и дифференциальная диагностика множественной миеломы. Вопр. онкол. 2004; 4: 406–16. [Bessmeltsev S.S. Diagnostika i differentsialnaya diagnostika mnozhestvennoy miyelomy (Detection and differential diagnosis of multiple myeloma. In: Issues of oncol.). Vopr. onkol. 2004; 4: 406–16.]
  83. Kyle R.A. Sequence of testing for monoclonal gammopathies: serum and urine assays. Pathol. Lab. Med. 1999; 123(2): 114–8.
  84. Drayson M., Tang L.X., Drew R. et al. Serum free light chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97(9): 2900–2.
  85. Dingli D., Kyle R.A., Rajkumar S.V. et al. Immunoglobulin free light chains and solitary plasmacytoma of bone. Blood 2006; 108(6): 1979–83.
  86. Dispenzieri A., Kyle R.A., Katzmann J.A. et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008; 111(2): 785–9.
  87. Katzmann J.A., Clark R.J., Abrahman R.S. et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Chem. 2002; 48: 1437–44.
  88. Smith A., Wisloff F., Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. J. Haematol. 2006; 132(4): 410–51.
  89. Kyle R.A., Rajkumar S.V. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23(1): 3–9.
  90. Rajkumar S.V., Dispenzieri A., Kyle R. Monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin. Proc. 2006; 81: 693–703.
  91. Drayson M., Tang L.X., Drew R. et al. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97: 2900–2.
  92. Rajkumar S.V., Kyle R.A., Therneau T.M. et al. Serum free light ration is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005; 106(3): 812–7.
  93. Kyle R.A. Monoclonal gammopathy of undetermined significance and solitary plasmacytoma: implications for progression to overt multiple myeloma. Oncol. Clin. N. Am. 1997; 11: 71–87.
  94. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. J. Haematol. 2003; 121(5): 749–57.
  95. Kyle R.A., Greipp P.R. ‘Idiopathic’ Bence Jones proteinuria: long-term follow-up in seven patients. Engl. J. Med. 1982; 306: 564–7.
  96. Diop P.A., Haudrechy D., Sylla-Niang M. et al. Laboratory diagnosis of monoclonal gammopathies. Prospective study of 14 cases in Dakar, Senegal. Bull. Soc. Pathol. 1998; 91: 242–6.
  97. Sezer O., Heider U., Zavrski I., Possinger K. Differentiation of monoclonal gammopathy of undetermined significance and multiple myeloma using flow cytometric characteristics of plasma cells. Haematologica 2001; 86: 837–43.
  98. Gandara D.R., Mackenzie M.R. Differential diagnosis of monoclonal gammopathy. Clin. N. Am. 1988; 72(5): 1155–68.
  99. Weber D., Wang L.M., Delasalle K. et al. Risk factors for early progression of asymptomatic multiple myeloma. Hematology J. 2003; 4(Suppl. 1): S31.
  100. Cesana C., Klersy C., Barbarano L. et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J. Clin. Oncol. 2002; 20: 1625–34.
  101. Vachon C.M., Kyle R.A., Therneau N.M. et al. Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood 2009; 114: 785–7.
  102. Rajkumar S.V., Kyle R.A., Buadj F.K. Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence. Mayo Clin. Proc. 2010; 85(10): 945–8.
  103. Kyle R.A., Therneau T.M., Rajkumar S.V. et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N. Engl. J. Med. 2002; 346: 564–9.
  104. Landgren O., Kyle R.A., Pfeiffer R.M. et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009; 113(22): 5412–5.
  105. Weiss B.M., Abadie J., Verma P. et al. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 2009; 113(22): 5418–21.
  106. Kyle R.A., Remstein E., Therneau T.M. et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N. Engl. J. Med. 2007; 356: 2582–90.
  107. Moulopoulos L.A., Dimopoulos M.A., Weber D. et al. Magnetic resonance imaging in the staging of solitary plasmacytoma of bone. J. Clin. Oncol. 1993; 11: 1311–5.
  108. Tsang R.W., Gospodarowicz M.K., Pintilie M. et al. Solitary plasmacytoma treated with radiotherapy: Impact of tumor size on outcome. Intern. J. Rad. Oncol. Biol. Phys. 2011; 50: 113–20.
  109. Knowling M.A., Harwood A.R., Bergsagel D.E. Comparison of extramedullary plasmacytomas with solitary and multiple plasma cell tumors of bone. J. Clin. Oncol. 1983; 1: 255–62.
  110. Alexiou C., Kau R.J., Dietzfelbinger H. et al. Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts. Cancer 1999; 85: 2305–14.
  111. McKenna R.W., Kyle R.A., Kuehl W.M. et al. Plasma cell neoplasms. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Ed. by S.H. Swerdlow, E. Campo, N.L. Harris et al., 4th ed. Lyon: IARC Press, 2008: 200–13.
  112. Costello R., Sainty D., Bouabdallah R. et al. Primary plasma cell leuukemia: a report of 18 cases. Leuk. Res. 2001; 25: 103–7.
  113. Vela-Ojeda J., Garcia-Ruiz Esparza M.A., Rosas-Cabral A. et al. Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia. Ann. Hematol. 2002; 81: 362–7.
  114. Lebovic D., Zhang L., Alsina M. et al. Clinical Outcomes of Patients With Plasma Cell Leukemia in the Era of Novel Therapies and Hematopoietic Stem Cell Transplantation Strategies: A Single-Institution Experience. Clin. Lymph. Myel. Leuk. 2012; 11(6): 507–11.
  115. Gutierez N.C., Hernandez J.M., Garcia J.L. et al. Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization. Leukemia 2001; 5: 840–5.
  116. Tiedemann R.E., Gonzalez-Paz N., Kyle R.A. et al. Genetic aberrations and survival in plasma cell leukemia. Leukemia 2008; 22: 1044–52.
  117. Chang H., Qi X., Yeung J. et al. Genetic aberrations including chromosome 1 abnormalities and clinical features of plasma cell leukemia. Leuk. Res. 2009; 33: 259–62.
  118. Dierlamm T., Laack E., Dierlamm J. IgM myeloma: a report of four cases. Ann. Hematol. 2002; 81: 136–9.
  119. Owen R.G., Treon S.P., Al-Katib A. et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Semin. Oncol. 2003; 30(2): 110–5.
  120. Gertz M.A. Waldenstrom macroglobulinemia: 2011 update on diagnosis, risk stratification, and management. J. Hematol. 2011; 86(5): 411–6.
  121. Криволапов Ю.А., Леенман Е.Е. Морфологическая диагностика лимфом. СПб.: Издательско-полиграфическая компания «Коста», 2006.
  122. Krivolapov Yu.A., Leyenman Ye.Ye. Morfologicheskaya diagnostika limfom (Morphologic diagnosis of lymphomas). Spb.: Izdatelskopoligraficheskaya kompaniya «Kosta», 2006.
  123. Kyle R.A., Treon S.P., Alexanian R. et al. Prognostic markers and criteria to initiate therapy in Waldenstrom’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia [review]. Oncol. 2003; 30(2): 116–20.
  124. Михайлов А.М., Бессмельцев С.С., Пожарисский К.М. и др. Болезнь Кастлемана и POEMS-синдром, их проявления и взаимосвязь. В кн.: Редкие гематологические болезни и синдромы. Под ред. М.А. Волковой. М.: Практическая медицина, 2011: 360–83. [Mikhaylov A.M., Bessmeltsev S.S., Pozharisskiy K.M. i dr. Bolezn Kastlemana i POEMS-sindrom, ikh proyavleniya i vzaimosvyaz. V kn.: Redkiye gematologicheskiye bolezni i sindromy. Pod red. M.A. Volkovoy (Castleman’s disease and POEMS syndrome, their presentation and interrelations. In: Rare hematological disorders and syndromes. Ed. by M.A. Volkova). : Prakticheskaya meditsina, 2011: 360–83.]
  125. Алексеев В.В. Диагностика и лечение болей в пояснице, вызванных компрессионной радикулопатией. Справ. поликлин. врача 2002; 4: 28–32. Alekseyev V.V. Diagnostika i lecheniye boley v poyasnitse, vyzvannykh kompressionnoy radikulopatiyey [Diagnosis and treatment of lower back pain caused by compression radiculopathy. In: Desk book of polycl. doctor]. Sprav. poliklin. vracha 2002; 4: 28–32.
  126. Балаболкин М.И. Эндокринология. М.: Универсум паблишинг, 1998. [Balabolkin M.I. Endokrinologiya (Endocrinology). : Universum pablishing, 1998.]
  127. Колондаев А.Ф., Балберкин А.Ф. Болезнь Педжета (деформиру- ющий остит). Врач 2003; 4: 13–6. [Kolondayev A.F., Balberkin A.F. Bolezn Pedzheta (deformiruyushchiy ostit) (Paget’s disease (osteitis deformans). In: Medical practitioner). Vrach 2003; 4: 13–6.]
  128. Васильев Ю.В. Боль за грудиной: дифференциальная диагностика и лечение. Consilium medicum (Приложение). 2002; 3: 3–5. [Vasilyev Yu.V. Bol za grudinoy: differentsialnaya diagnostika i lecheniye (Retrosternal pain, differential diagnosis and treatment. In: Consilium medicum (Addendum)). Consilium medicum (Prilozheniye). 2002; 3: 3–5.]
  129. Бессмельцев С.С. Клиническая трактовка увеличенной скорости оседания эритроцитов практикующим врачом (Часть 1). Вестн. гематол. 2005; 2: 54–62. [Bessmeltsev S.S. Klinicheskaya traktovka uvelichennoy skorosti osedaniya eritrotsitov praktikuyushchim vrachom (Chast 1) (Clinical interpretation of elevated erythrocyte sedimentation rate by medical practitioner (Part I). In: Hematol. bullet.). Vestn. gematol. 2005; 2: 54–62.]
  130. Coleman R.E. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat. Rev. 2001; 27: 165–76. 131. Mundy G.R. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat. Rev. Cancer 2002; 2: 584–93. 132. Fukutomi M. Increased incidence of bone metastases in hepatocellular carcinoma. J. Gastroenterol. Hepatol. 2001; 13: 1083–8.

 

Эпигенетика в онкогематологии: краткий реферативный обзор

ОБЗОРЫ , , , ,

Ширин А.Д., Калетин Г.И., Баранова О.Ю.

ФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина», Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Ширин Антон Дмитриевич, канд. мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-28-24; e-mail: shirin-anton@mail.ru

Для цитирования: Ширин А.Д., Калетин Г.И., Баранова О.Ю. Эпигенетика в онкогематологии: краткий реферативный обзор. Клиническая онкогематология. 2015;8(1):26–30.

РЕФЕРАТ

Цель. Рассмотреть исторические аспекты эпигенетики как самостоятельного направления биологии, а также осветить вопросы посттрансляционных модификаций ДНК и гистонов (PTM) в качестве эпигенетических событий.

Методы. Обзор основных положений эпигенетики в актуальных статьях и рефератах: метилирование ДНК, ацетилирование, фосфорилирование, убиквитинирование и сумоилирование гистонов в процессах возникновения онкологических заболеваний. К настоящему времени большой интерес вызвало влияние на эпигенетические процессы так называемой интерферирующей РНК. РНК-интерференция (RNAi) может использоваться для выявления эпигенетических регуляторов с целью потенциального фармакологического воздействия на опухолевые клетки. В работе рассматривается роль малых молекул I-BET и JQ1 в противоопухолевом ответе. Отдельно изучается значение BET-белков при онкогематологических заболеваниях.

Выводы. На сегодняшний день в лечении некоторых опухолей системы крови применяются ингибиторы ДНК-метилтрансферазы (гипометилирующие агенты) и ингибиторы гистондеацетилазы, которые представляют собой новое направление — эпигенетическую терапию.

Ключевые слова: эпигенетика, РНК-интерференция, BET-белки, метилирование, деацетилирование.

Получено: 2 декабря 2014 г.

Принято в печать: 12 декабря 2014 г.

Читать статью в PDFpdficon

ЛИТЕРАТУРА

  1. Уоддингтон К.Х. Основные биологические концепции. В кн.: На пути к теоретической биологии. Часть I. Пролегомены. М.: Мир, 1970:11–38. [Waddington CH. Basic ideas of biology. In: Waddington CH, ed. Na puti k teoreticheskoi biologii. Chast’ I. Prolegomeny. (Towards a theoretical biology. Part I. Prolegomena.) Moscow: Mir Publ.; 1970. pp. 11–38. (In Russ)]
  2. Shannon K, Armstrong SA. Genetics, epigenetics, and leukemia. N Engl J Med. 2010;363(25):2460–1. doi: 10.1056/NEJMe1012071.
  3. Ayton PM, Cleary ML. Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene Rev. 2001;20(40):5695–707. doi: 10.1038/sj.onc.1204639.
  4. Daser A, Rabbitts TH. Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis. Genes Dev. 2004;18(9):965–74. doi: 10.1101/gad.1195504.
  5. Manodoro F, Marzec J, Chaplin T, et al. Loss of imprinting at the 14q32 domain is associated with microRNA overexpression in acute promyelocytic leukemia. Blood. 2014;123(13):2066–74. doi: 10.1182/blood-2012-12-469833.
  6. Huntly BJP, Johnson PWM. Targeting Epigenetic Readers in Hematologic Malignancies: A Good BET? The Hematologist. 2012;10(2). http://www.hematology.org/Thehematologist/Mini-Review/1181.aspx.
  7. Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem. 2007;282(18):13141–5. doi: 10.1074/jbc.r700001200.
  8. Fowler T, Sen R, Roy AL. Regulation of primary response genes. Mol Cell. 2011;44(3):348–60. doi: 10.1016/j.molcel.2011.09.014.
  9. Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature. 2010;468(7327):1067–73. doi: 10.1038/nature09504.
  10. Nicodeme E, Jeffrey KL, Schaefer U, et al. Suppression of inflammation by a synthetic histone mimic. Nature. 2010;468(7327):1119–23. doi: 10.1038/nature09589.
  11. Dawson MA, Prinjha RK, Dittmann A, et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011;478(7370):529–33. doi: 10.1038/nature10509.
  12. Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 2011;25(7):661–72. doi: 10.1101/gad.2015411.
  13. Zuber J, Shi J, Wang E, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478(7370):524–8. doi: 10.1038/nature10334.
  14. Delmore JE, Issa GC, Lemieux ME, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904–17. doi: 10.1016/j.cell.2011.08.017.
  15. Mertz JA, Conery AR, Bryant BM, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA. 2011;108(40):16669–74. doi: 10.1073/pnas.1108190108.
  16. Thompson CB. Targeting Metabolic Inputs into Epigenetic Regulations of Acute Leukemia. Blood. 2013;122: Abstract SCI-26.
  17. http://medbiol.ru/medbiol/epigenetica/0005e8fd.htm.
  18. http://moikompas.ru/compas/modification_histones.
  19. Mai A, Altucci L. Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead. Int J Biochem Cell Biol. 2009;41(1):199–213. doi: 10.1016/j.biocel.2008.08.020.
  20. Чехун В. Эпигенетика рака. Колонка главного редактора. Онкология. 2008;10(3):301–2. [Chekhun V. Epigenetics of cancer. Editorial column. Onkologiya. 2008;10(3):301–2. (In Russ)]
  21. http://moikompas.ru/compas/avaiserman.

Современные аспекты применения позитронно-эмиссионной томографии при лимфомах

ОБЗОРЫ , , ,

Асланиди И.П., Мухортова О.В., Катунина Т.А., Екаева И.В., Шавман М.Г.

ФГБНУ «Научный центр сердечно-сосудистой хирургии им. А.Н. Бакулева», Рублевское ш., д. 135, Москва, Российская Федерация, 121552

Для переписки: Ольга Валентиновна Мухортова, д-р мед. наук, Рублевское ш., д. 135, Москва, Российская Федерация, 121552; тел.: +7(495)414-77-31; e-mail: olgamukhortova@yandex.ru

Для цитирования: Асланиди И.П., Мухортова О.В., Катунина Т.А. и др. Современные аспекты применения позитронно-эмиссионной томографии при лимфомах. Клиническая онкогематология. 2015;8(1):13–25.

РЕФЕРАТ

Цель. Определить наиболее эффективные направления использования позитронно-эмиссионной томографии (ПЭТ) со фтордезоксиглюкозой, меченной 18-фтором (18F-ФДГ), у больных лимфомами.

Методы. Изучено 56 научных источников, опубликованных в 2005–2014 гг., в которых анализируются результаты последних крупных исследований по применению ПЭТ у больных лимфомами.

Результаты. ПЭТ с 18F-ФДГ стала неотъемлемой частью диагностического алгоритма у больных лимфомами, которые характеризуются активным накоплением 18F-ФДГ. Высокая точность ПЭТ у пациентов с некоторыми типами лимфом позволяет эффективно использовать метод в клинической практике для определения стадии заболевания, оценки эффективности лечения, уточнения распространенности рецидива, результатов противорецидивного лечения, а также при подозрении на трансформацию лимфомы. Применение ПЭТ на других этапах лечения больных лимфомами находится в процессе научных разработок. При индолентных лимфомах с известной низкой гликолитической активностью или лимфомах редких гистологических типов ПЭТ для оценки эффективности лечения используется только при наличии исходных (до начала лечения) результатов исследования. Для оценки результатов лечения рекомендуется использовать 5-балльную шкалу Deauville. Соблюдение сроков обследования в процессе противоопухолевой терапии позволяет существенно повысить точность ПЭТ-диагностики. Одиночные очаги, выявленные при ПЭТ и имеющие принципиальное значение для выбора лечения, должны быть верифицированы другими методами диагностики. Выполнение ПЭТ при наблюдении за больными в состоянии ремиссии признается нецелесообразным.

Выводы. ПЭТ является «золотым стандартом» стадирования и оценки эффективности лечения больных лимфомами, которые характеризуются активным накоплением 18F-ФДГ.

Ключевые слова: ПЭТ, лимфомы, международные рекомендации, 5-балльная шкала Deauville.

Получено: 14 ноября 2014 г.

Принято в печать: 18 ноября 2014 г.

Читать статью в PDFpdficon

ЛИТЕРАТУРА

  1. Wood KA, Hoskin PJ, Saunders MI. Positron Emission Tomography in Oncology: A Review. Clin Oncol. 2007;19(4):237–55. doi: 10.1016/j.clon.2007.02.001.
  2. Cheson BD. Role of functional imaging in the management of lymphoma. J Clin Oncol. 2011;29(14):1844–54. doi: 10.1200/jco.2010.32.5225.
  3. Collins CD. PET in lymphoma. Cancer Imaging. 2006;6:S63–S70. doi: 10.1102/1470-7330.2006.9013.
  4. Boellaard R, O’Doherty MJ, Weber WA, et al. FDG PET and PET/CT: EANM procedure guidelines for tumor PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(7):181–200. doi: 10.1007/s00259-010-1459-4.
  5. Weiler-Sagie M, Bushelev O, Epelbaum R, et al. (18)F-FDG avidity in lymphoma readdressed: A study of 766 patients. J Nucl Med. 2010;51(1):25–30. doi: 10.2967/jnumed.109.067892.
  6. Kostakoglu L, Cheson D. State-of-the-art research on Lymphomas: role of molecular imaging for staging, prognostic evaluation, and treatment response. Front Oncol. 2013;3:212. doi: 10.3389/fonc.2013.00212.
  7. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. J Clin Oncol. 2014;32(27):3059–67. doi: 10.1200/jco.2013.54.8800.
  8. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of Imaging in the Staging and Response Assessment of Lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048–58. doi: 10.1200/jco.2013.53.5229.
  9. Engert A, Haverkamp H, Kobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): A randomised, open-label, phase 3 non-inferiority trial. The Lancet. 2012;379(9828):1791–9. doi: 10.1016/s0140-6736(11)61940-5.
  10. Thomson KJ, Kayani I, Ardeshna K, et al. A response-adjusted PET-based transplantation strategy in primary resistant and relapsed Hodgkin lymphoma. Leukemia. 2013;27(6):1419–22. doi: 10.1038/leu.2012.318.
  11. Hutchings M. FDG-PET response-adapted therapy: is 18F-fluorodeoxyglucose positron emission tomography a safe predictor for a change of therapy? Hematol Oncol Clin North Am. 2014;28(1):87–103. doi: 10.1016/j.hoc.2013.10.008.
  12. Radford J, Barrington S, Counsell N, et al. Involved field radiotherapy vs no further treatment in patients with clinical stages IA and IIA Hodgkin lymphoma and a ‘negative’ PET scan after 3 cycles ABVD: results of the UK NCRI RAPID trial. Blood. 2012;120(21):547.
  13. Barrington SF, Mikhaeel NG. When should FDG-PET be used in the modern management of lymphoma? Br J Haematol. 2014;164(3):315–28. doi: 10.1111/bjh.12601.
  14. Omur O, Baran Y, Oral A, et al. Fluorine-18 fluorodeoxyglucose PET-CT for extranodal staging of non-Hodgkin and Hodgkin lymphoma. Diagn Interv Radiol. 2014;20(2):185–92. doi: 10.5152/dir.2013.13174.
  15. Luminari S, Biasoli I, Arcaini L, et al. The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: A retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi. Ann Oncol. 2013;24(8):2108–12. doi: 10.1093/annonc/mdt137.
  16. Pelosi E, Pregno P, Penna D, et al. Role of whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDGPET/CT) and conventional techniques in the staging of patients with Hodgkin and aggressive non Hodgkin lymphoma. Radiol Med. 2008;113(4):578–90. doi: 10.1007/s11547-008-0264-7.
  17. Casulo C, Schoder H, Feeney J, et al. FDG PET in the staging and prognosis of T cell lymphoma. Leuk Lymphoma. 2013;54(10):2163–7. doi: 10.3109/10428194.2013.767901.
  18. Scott AM, Gunawardana DH, Wong J, et al. Positron emission tomography changes management, improves prognostic stratification and is superior to gallium scintigraphy in patients with low-grade lymphoma: results of a multicentre prospective study. Eur J Nucl Med Mol Imaging. 2009;36(3):347–53. doi: 10.1007/s00259-008-0958-z.
  19. Cortes-Romera M, Sabate-Llobera A, Mercadal-Vilchez S, et al. Bone marrow evaluation in initial staging of lymphoma: 18F-FDG PET/CT versus bone marrow biopsy. Clin Nucl Med. 2014;39(1):e46–52. doi: 10.1097/rlu.0b013e31828e9504.
  20. Adams HJ, Kwee TC, Vermoolen MA, et al. Whole-body MRI for the detection of bone marrow involvement in lymphoma: prospective study in 116 patients and comparison with FDG-PET. Eur Radiol. 2013;23(8):2271–8. doi: 10.1007/s00330-013-2835-9.
  21. Castellucci P, Nanni C, Farsad M, et al. Potential pitfalls of 18F-FDG PET in a large series of patients treated for malignant lymphoma: prevalence and scan interpretation. Nucl Med Comm. 2005;26(8):689–94. doi: 10.1097/01.mnm.0000171781.11027.bb.
  22. Storto G, Di Giorgio E, De Renzo A, et al. Assessment of metabolic activity by PET-CT with F-18-FDG in patients with T-cell lymphoma. Br J Haematol. 2010;151(2):195–7. doi: 10.1111/j.1365-2141.2010.08335.x.
  23. Ansell SM, Armitage JO. Positron Emission Tomographic Scans in Lymphoma: Convention and Controversy. Mayo Clin Proc. 2012;87(6):571–80. doi: 10.1016/j.mayocp.2012.03.006.
  24. Araf S, Montoto S. The use of interim 18F-fluorodeoxyglucose PET to guide therapy in lymphoma. Fut Oncol. 2013;9(6):807–15. doi: 10.2217/fon.13.55.
  25. Zinzani PL, Rigacci L, Stefoni V, et al. Early interim 18F-FDG PET in Hodgkin’s lymphoma: Evaluation on 304 patients. Eur J Nucl Med Mol Imaging. 2012;39(1):4–12. doi: 10.1007/s00259-011-1916-8.
  26. Moulin-Romsee G, Hindie E, Cuenca X, et al. (18) F-FDG PET/CT bone/bone marrow findings in Hodgkin’s lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging. Eur J Nucl Med Mol Imaging. 2010;37(6):1095–105. doi: 10.1007/s00259-009-1377-5.
  27. Hamilton R, Andrews I, McKay P, et al. Loss of utility of bone marrow biopsy as a staging evaluation for Hodgkin lymphoma in the positron emission tomography-computed tomography era: a West of Scotland study. Leuk Lymphoma. 2014;55(5):1049–52. doi: 10.3109/10428194.2013.821201.
  28. Berthet L, Cochet A, Kanoun S, et al. In newly diagnosed diffuse large B-cell lymphoma, determination of bone marrow involvement with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification than does biopsy. J Nucl Med. 2013;54(8):1244–50. doi: 10.2967/jnumed.112.114710.
  29. El-Galaly TC, d’Amore F, Mylam KJ, et al. Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma. J Clin Oncol. 2012;30(36):4508–14. doi: 10.1200/jco.2012.42.4036.
  30. El-Galaly TC, Hutchings M, Mylam KJ, et al. Impact of 18F-FDG PET/CT Staging in Newly Diagnosed Classical Hodgkin Lymphoma: Less Cases with Stage I Disease and More with Skeletal Involvement. Leuk Lymphoma. 2014;55(10):2349–55. doi: 10.3109/10428194.2013.875169.
  31. Cheng G, Alavi A. Value of 18F-FDG PET versus iliac biopsy in the initial evaluation of bone marrow infiltration in the case of Hodgkin’s disease: a meta-analysis. Nucl Med Commun. 2013;34(1):25–31. doi: 10.1097/mnm.0b013e32835afc19.
  32. Chen YK, Yeh CL, Tsui CC, et al. F-18 FDG PET for evaluation of bone marrow involvement in non-Hodgkin lymphoma: A meta-analysis. Clin Nucl Med. 2011;36(7):553–9. doi: 10.1097/rlu.0b013e318217aeff.
  33. Мухортова О.В., Асланиди И.П., Шурупова И.В. и др. Применение позитронно-эмиссионной томографии для оценки поражения костного мозга у больных злокачественными лимфомами. Медицинская радиология и радиационная безопасность. 2010;2:43–52.
    [Mukhortova OV, Aslanidi IP, Shurupova IV, et al. Use of positron emission tomography for assessment of bone marrow damage in patients with malignant lymphomas. Meditsinskaya radiologiya i radiatsionnaya bezopasnost’. 2010;2:43–52. (In Russ)]
  34. Kashyap R, Lau E, George A, et al. High FDG activity in focal fat necrosis: a pitfall in interpretation of posttreatment PET/CT in patients with non-Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2013;40(9):1330–6. doi: 10.1007/s00259-013-2429-4.
  35. Hutchings M, Barrington SF. PET/CT for Therapy Response Assessment in Lymphoma. J Nucl Med. 2009;50(Suppl 1):21S–30S. doi: 10.2967/jnumed.108.05719.
  36. Dabaja BS, Phan J, Mawlawi O, et al. Clinical implications of positron emission tomography – negative residual computed tomography masses after chemotherapy for diffuse large B-cell lymphoma. Leuk Lymphoma. 2013;54(12):2631–8. doi: 10.3109/10428194.2013.784967.
  37. Gallamini A, Barringtom S, Biggi A, et al. The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale. Haematologica. 2014;99(6):1107–13. doi: 10.3324/haematol.2013.103218.
  38. Fuertes S, Setoain X, Lopez-Guillermo A, et al. Interim FDG PET/CT as a prognostic factor in diffuse large B-cell lymphoma. Eur J Nucl Med Mol Imaging. 2013;40(4):496–504. doi: 10.1007/s00259-012-2320-8.
  39. Bodet-Milin C, Touzeau C, Leux C, et al. Prognostic impact of 18F-fluorodeoxyglucose positron emission tomography in untreated mantle cell lymphoma: a retrospective study from the GOELAMS group. Eur J Nucl Med Mol Imaging. 2010;37(9):1633–42. doi: 10.1007/s00259-010-1469-2.
  40. Cahu X, Bodet-Milin C, Brissot E, et al. 18F-fluorodeoxyglucose-positron emission tomography before, during and after treatment in mature T/NK lymphomas: a study from the GOELAMS group. Ann Oncol. 2011;22(3):705–11. doi: 10.1093/annonc/mdq415.
  41. Lee H, Kim SK, Kim YI, et al. Early Determination of Prognosis by Interim 3¢-Deoxy-3¢-18F-Fluorothymidine PET in Patients with Non-Hodgkin Lymphoma. J Nucl Med. 2014;55(2):216–22. doi: 10.2967/jnumed.113.124172.
  42. Le Dortz L, De Guibert S, Bayat S, et al. Diagnostic and prognostic impact of 18F-FDG PET/CT in follicular lymphoma. Eur J Nucl Med Mol Imaging. 2010;37(12):2307–14. doi: 10.1007/s00259-010-1539-5.
  43. Lopci E, Zanoni L, Chiti A, et al. FDG PET/CT predictive role in follicular lymphoma. Eur J Nucl Med Mol Imaging. 2012;39(5):864–71. doi: 10.1007/s00259-012-2079-y.
  44. Oki Y, Chuang H, Chasen B, et al. The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma. Br J Haematol. 2014;165(1):112–6. doi: 10.1111/bjh.12715.
  45. Bodet-Milin C, Eugene T, Gastinne T. FDG-PET in Follicular Lymphoma Management. J Oncol. 2012:370272. doi: 10.1155/2012/370272.
  46. Sucak GT, Ozkurt ZN, Suyani E, et al. Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival. Ann Hematol. 2011;90(11):1329–36. doi: 10.1007/s00277-011-1209-0.
  47. Biggi A, Gallamini A, Chauvie S, et al. International validation study for interim PET in ABVD-treated, advanced-stage Hodgkin lymphoma: Interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013;54(5):683–90. doi: 10.2967/jnumed.112.110890.
  48. Nols N, Mounier N, Bouazza S, et al. Quantitative and qualitative analysis of metabolic response at interim PET-scan combined with IPI is highly predictive of outcome in diffuse large B-cell lymphoma. Leuk Lymphoma. 2014;55(4):773–80. doi: 10.3109/10428194.2013.831848.
  49. Gallamini A, Kostakoglu L. Positron emission tomography/computed tomography surveillance in patients with lymphoma: a fox hunt? Haematologica. 2012;97(6):797–9. doi: 10.3324/haematol.2012.063909.
  50. Yoo C, Lee DH, Kim JE, et al. Limited role of interim PET/CT in patients with diffuse large B-cell lymphoma treated with R-CHOP. Ann Hematol. 2011;90(7):797–802. doi: 10.1007/s00277-010-1135-6.
  51. Pregno P, Chiappella A, Bello M, et al. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood. 2012;119(9):2066–73. doi: 10.1182/blood-2011-06-359943.
  52. Safar V, Dupuis J, Itti E, et al. Interim [18F]fluorodeoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy plus rituximab. J Clin Oncol. 2012;30(2):184–90. doi: 10.1200/JCO.2011.38.2648.
  53. Terasawa T, Dahabreh IJ, Nihashi T. Fluorine-18-Fluorodeoxyglucose positron emission tomography in response assessment before high-dose chemotherapy for lymphoma: a systematic review and meta-analysis. The Oncologist. 2010;15(7):750–9. doi: 10.1634/theoncologist.2010-0054.
  54. Sucak GT, Ozkurt ZN, Suyani E, et al. Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival. Ann Hematol. 2011;90(11):1329–36. doi: 10.1007/s00277-011-1209-0.
  55. Von Tresckow B, Engert A. The emerging role of PET in Hodgkin lymphoma patients receiving autologous stem cell transplant. Expert Rev Hematol. 2012;5(5):483–6. doi: 10.1586/ehm.12.41.
  56. Bodet-Milin C, Kraeber-Bodere F, Moreau P, et al. Investigation of FDG-PET/CT imaging to guide biopsies in the detection of histological transformation of indolent lymphoma. Haematologica. 2008;93(3):471–2. doi: 10.3324/haematol.12013.