bone marrow

Role of Defects of Hematopoietic and Lymphoid Niches in Genesis of Chronic Lymphocytic Leukemia

LYMPHOID TUMORS , , , , ,

NYu Semenova, SS Bessmel’tsev, VI Rugal’

Russian Scientific Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Natal’ya Yur’evna Semenova, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-09-95; e-mail: sciencerugal@gmail.com

For citation: Semenova NYu, Bessmel’tsev SS, Rugal’ VI. Role of Defects of Hematopoietic and Lymphoid Niches in Genesis of Chronic Lymphocytic Leukemia. Clinical oncohematology. 2016;9(2):176–90 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-176-190

ABSTRACT

Background & Aims. Niche-forming elements of the bone marrow and lymphoid organs play an important role in the pathogenesis of chronic lymphocytic leukemias. The aim is to determine multifunctional characteristics of stromal elements of the hematopoietic and lymphoid microenvironment involved in formation of a niche of hematopoietic stem cells and lymphoid precursor cells.

Methods. Histological specimens of the bone marrow and lymph nodes of 112 CLL patients (64 men and 48 women) were investigated. 45 patients were included in the combined analysis group. The age median was 60 years. 50 volunteers were included in the control group: trepanobiopsy of the iliac area was performed in 30 healthy subjects, and lymph node biopsy was performed in 20 patients with reactive lymphadenopathy. Standard staining (hematoxylin-eosin, azure-II-eosin, silver impregnation, Masson stain) was used for histological studies. The immunohistochemical analysis was performed using the primary antibody panel and the polymer visualization system Dako according to staining protocol.

Results. While analyzing 96 trepanobioptates, we isolated three types of bone marrow infiltration: nodular (18.8 %, n = 18), interstitial (27 %, n = 26) and diffuse (54.2 %, n = 52). Nodular and interstitial bone marrow infiltrations reflect a more favorable course of CLL as compared to the diffuse type. The morphological characteristics of the bone marrow stroma of CLL patients may be caused by both primary impairment of the hematopoietic microenvironment, and cytokine disbalance resulting from the effect on the stroma of the leukemic clone. The morphological examination of lymph node bioptate of CLL patients demonstrated impairment of histoarchitectonics of lymphoid tissue elements in all cases. In lymph nodes of CLL patients, we demonstrated the increased number of small vessels on the background of decreased expression of extracellular matrix protein expression: IV type collagen, laminin, and desmin. Disintegration of lymph node follicular dendritic cells network was demonstrated.

Conclusion. Examination of the nature of the effect of stroma on hematopoiesis remains an urgent hematological problem. In order to solve the problem of regulatory influence, the use of morphological methods is recommended, including the immunohistochemical analysis.

Keywords: hematopoietic stem cell, bone marrow, hematopoietic stem cell niche, microenvironment, lymphoid niche, follicular dendritic cells.

Received: October 8, 2015

Accepted: January 10, 2016

Read in PDF (RUS)pdficon

REFERENCES

  1. Ругаль В.И. Морфофункциональная характеристика стромы костного мозга в норме и при остром миелобластном лейкозе: Автореф. дис. ¼ д-ра мед. наук. Л., 1989.
    [Rugal’ VI. Morfofunkcionalnaja harakteristika stromy kostnogo mozga v norme i pri ostrom mieloblastnom lejkoze. (Morphofunctional characteristics of the bone marrow stroma in normal persons and in patients with acute mieloblastic leukemia.) [dissertation] Leningrad; 1989. (In Russ)]
  2. Krause D, Scadden D, Preffer L. The Hematopoietic Stem Cell Niche — Home for Friend and Foe. Clin Cytometry. 2012;58(7):7–20. doi: 10.1002/cyto.b.21066.
  3. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005;352(8):804–15. doi: 10.1056/nejmra041720.
  4. Rawstron AC, Bennett FL, O’Connor SJ, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359(6):575–83. doi: 10.1056/NEJMoa075290.
  5. Asplund SL, McKenna RW, Howard M, Croft SH. Immunophenotype does not correlate with lymph node gistology in chronic lymphocytic leukemia/small lymphocytic lymphoma. Am J Surg Pathol. 2002;26(5):624–9. doi: 10.1097/00000478-200205000-00008.
  6. Montillo M, Hamblin T, Hallek M, et al. Chronic lymphocytic leukemia: novel prognostic factors and their relevance for risk-adapted therapeutic strategies Haematologica. 2005;90(3):391–9.
  7. Бакиров Б.А. Клинико-патогенетическая характеристика и факторы прогноза в развитии и течении хронического лимфолейкоза: Автореф. ¼ д-ра мед. наук. СПб., 2013.
    [Bakirov BA. Kliniko-patogeneticheskaja harakteristika i faktory prognoza v razvitii i techenii hronicheskogo limfoleikoza. (Clinico-pathological characteristics and prognostic factors in development and course of chronic lymphocytic leukemia.) [dissertation] Saint Petersburg; 2013. (In Russ)]
  8. Hallek M, Cheson BD, Cotovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute Working Group 1996 guidelines. Blood. 2008;111(12):544–6. doi: 10.1182/blood-2007-06-093906.
  9. Бессмельцев С.С., Абдулкадыров К.М. Флударабин в терапии различных вариантов неходжкинских лимфом. Современная онкология. 2011;13(4):13–9.
    [Bessmeltsev SS, Abdulkadirov KM. Fludarabine in treatment different variants non-Hodgkin’s lymphoma. Sovremennaya onkologiya. 2011;13(4):13–9. (In Russ)]
  10. Бессмельцев С.С. Современные методы диагностики и лечения больных хроническим лимфолейкозом. Вестник гематологии. 2011;1:137–56.
    [Bessmel’tsev SS. Modern methods of diagnosis and treatment of patients with chronic lymphocytic leukemia. Vestnik gematologii. 2011;1:137–56. (In Russ)]
  11. Семенова Н.Ю. Морфологические особенности интрамедуллярных стромальных структур гемопоэтической ниши и элементов лимфоидной стромы при хроническом лимфолейкозе: Дис. ¼ канд. биол. наук. СПб., 2015.
    [Semenova NYu. Morfologicheskie osobennosti intramedullyarnykh stromal’nykh struktur gemopoeticheskoi nishi i elementov limfoidnoi stromy pri khronicheskom limfoleikoze. (Morphological features of intramedullary stromal structures of hematopoietic niche and elements of the lymphoid stroma in chronic lymphocytic leukemia.) [dissertation] Saint Petersburg; 2015. (In Russ)]
  12. Amin S, Parker A, Manu J. Zap 70 in chronic lymphocytic leukemia. Int J Biochem Cell Biol. 2008;40(9):1654–8. doi: 10.1016/j.biocel.2007.05.016.
  13. Wolowiec D, Wozniak Z, Potoczek S. Bone marrow angiogenesis and proliferation in B-cell chronic lymphocytic leukemia. Anal Quant Cytol Histol. 2004;26(5):263–70.
  14. Чертков И.Л., Гуревич О.А. Стволовая кроветворная клетка и ее микроокружение. М., 1984. 238 с.
    [Chertkov IL, Gurevich ОА. Stvolovaya krovetvornaya kletka i ee mikrookruzhenie. (Hematopoietic stem cell and its microenvironment). Мoscow; 1984. 238 p. (In Russ)]
  15. Mayani H, Guilbert LJ, Janowaska-Wieczorek A. Biology of the hemopoietic microenvironment. Eur J Haematol. 1992;49(5):225–33. doi: 10.1111/j.1600-0609.1992.tb00053.x.
  16. Gothard D, Greenhough J, Ralph E. Prospective isolation of human bone marrow stromal cell subsets: A comparative study between Stro-1-, CD146- and CD105-enriched populations. J Tissue Eng. 2014;5(0): doi: 10.1177/2041731414551763.
  17. Purton LE, Scadden DT. The hematopoietic stem cell niche. StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute; 2008. pp. 1–14. doi: 10.3824/stembook.1.28.1.
  18. Taichman RS, Reilly MJ, Emerson SG. The hematopoietic microenvironment: osteoblasts and the hematopoietic microenvironment. Hematology. 2000;4(5):421–6.
  19. Scadden DT. The stem cell niche in health and leukemic disease. Best Pract Res Clin Haematol. 2007;20(1):19–27. doi: 10.1016/j.beha.2006.11.001.
  20. Семенова Н.Ю., Бессмельцев С.С., Ругаль В.И. Биология ниши гемопоэтических стволовых клеток. Клиническая онкогематология. 2014;7(4):501–10.
    [Semenova NYu, Bessmel’tsev SS, Rugal’ VI. Biology of hematopoietic stem cell niche. Klinicheskaya onkogematologiya. 2014;7(4):501–10. (In Russ)]
  21. Zhang J, Li L. Stem cell niche: microenvironment and beyond. J Biol Chem. 2008;283(15):9499–503. doi: 10.1074/jbc.R700043200.
  22. Бессмельцев С.С. Множественная миелома (патогенез, клиника, диагностика, дифференциальный диагноз). Часть 1. Клиническая онкогематология. 2013;6(3):237–58.
    [Bessmeltsev SS. Multiple myeloma (pathogenesis, clinical features, diagnosis, differential diagnosis). Part I. Klinicheskaya onkogematologiya. 2013;6(3):237–58. (In Russ)]
  23. Ругаль В.И., Бессмельцев С.С., Семенова Н.Ю. и др. Структурные особенности паренхимы и стромы костного мозга больных множественной миеломой. Биомедицинский журнал Medline.ru. 2012;13:515–523.
    [Rugal VI, Bessmeltsev SS, Semenova NYu, et al. Parenchyma and stroma bone marrow structural features in patients with multiple myeloma. Biomeditsinskii zhurnal Medline.ru. 2012;13:515–23. (In Russ)]
  24. Duhrsen U, Hossfeld DK. Stromal abnormalities in neoplastic bone marrow diseases. Ann Hematol. 1996;73(2):53–70. doi: 10.1007/s002770050203.
  25. Weisberg E, Azab AK, Manley PW, et al. Inhibition of CXCR4 in CML cells disrupts their interaction with the bone marrow microenvironment and sensitizes them to nilotinib. Leukemia. 2012;26(5):985–90. doi: 10.1038/leu.2011.360.
  26. Белянин В.Л., Цыплаков Д.Э. Диагностика реактивных гиперплазий лимфатических узлов. СПб., Казань, 1999. 328 с.
    [Belyanin VL, Tsyplakov DE. Diagnostika reaktivnykh giperplazii limfaticheskikh uzlov. (Diagnosis of reactive hyperplasia of lymph nodes.) Saint Petersburg, Kazan; 1999. 328 p. (In Russ)]
  27. Киселева М.В. Морфо-функциональное состояние стромы лимфатических узлов при некоторых лимфопролиферативных заболеваниях: Автореф. дис. ¼ канд. мед. наук. СПб., 2001.
    [Kiseleva MV. Morfo-funktsionalnoe sostoyanie stromy limfaticheskikh uzlov pri nekotoryh limfoproliferativnykh zabolevaniyah. (Morphofunctional state of the stroma of lymph nodes in certain lymphoproliferative diseases.) [dissertation] Saint Petersburg; 2001. (In Russ)]
  28. Chen L, Apgar J, Huynh L, et al. ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia. Blood. 2005;105(5):2036–41. doi: 10.1182/blood-2004-05-1715.
  29. Коган Е.А. Автономный рост и прогрессия опухолей. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2002;12(4):45–9.
    [Kogan EA. Autonomous growth and progression of tumors. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii. 2002;12(4):45–9. (In Russ)]
  30. Криволапов Ю.А., Леенман Е.Е. Морфологическая диагностика лимфом. СПб.: Коста, 2006. С. 45–8.
    [Krivolapov YuA, Leenman EE. Morfologicheskaya diagnostika limfom. (Morphological diagnostics of lymphomas.) Saint Petersburg: Kosta Publ.; 2006. pp. 45–8. (In Russ)]
  31. Мухина М.С., Пожарисский К.М., Леенман Е.Е. и др. Место дендритных клеток в микроокружении при лимфоме Ходжкина. Архив патологии. 2010;2:3–7.
    [Mukhina MS, Pozharisskii KM, Leenman EE, et al. Place of dendritic cells in the microenvironment in Hodgkin lymphoma. Arkhiv patologii. 2010;2:3–7. (In Russ)]
  32. Park CS, Choi YS. How do follicular dendritic cells interact intimately with B cells in the germinal centre. Immunology. 2005;114(1):2–10. doi: 10.1111/j.1365-2567.2004.02075.x.
  33. 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. doi: 10.1182/blood-2010-05-284984.
  34. Cordone I, Matutes E, Catovsky D. Monoclonal antibody Ki-67 identifies B and T cells in cycle in chronic lymphocytic leukemia: correlation with disease activity. Leukemia. 1992;6(9):902–6.
  35. Tavassoli M, Fridenstein A. Hemopoietic stromal microenvironment. Am J Hematol. 1983;15(2):195–203. doi: 10.1002/ajh.2830150211.
  36. Nagasawa T, Omatsu Y, Sugiyama T. Control of hematopoietic stem cells by the bone marrow stromal niche: the role of reticular cells. Trends Immunol. 2011;32(7):315–20. doi: 10.1016/j.it.2011.03.009.
  37. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132(4):631–44. doi: 10.1016/j.cell.2008.01.025.
  38. Yin T, Li L. The stem cell niches in bone. J Clin Invest. 2006;116(5):1195–201. doi: 10.1172/jci28568.
  39. Wei J, Wunderlich M, Fox C, et al. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell. 2008;13(6):483–95. doi: 10.1016/j.ccr.2008.04.020.
  40. Westen H, Beinton DF. Association of alkaline-phosphatase-positive reticulum cells in bone marrow granulocytic precursors. Exp Med. 1979;150(4):919–37. doi: 10.1084/jem.150.4.919.
  41. Taichman RS, Emerson SG. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J Exp Med. 1994;179(5):1677–82. doi: 10.1084/jem.179.5.1677.
  42. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425(6960):836–41. doi: 10.1038/nature02041.
  43. Tokoyoda K, Egawa T, Sugiyama T, et al. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004;20(6):707–18. doi: 10.1016/j.immuni.2004.05.001.
  44. Дризе Н.И. Различия между лейкозными и нормальными кроветворными стволовыми клетками. Онкогематология. 2006;1(2):5–9.
    [Drize NI. Difference between leukemic and normal hematopoietic stem cells. Onkogematologiya. 2006;1(2):5–9. (In Russ)]
  45. Mraz M, Zent CS, Church AK, et al. Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin alpha-4-beta-1 (VLA-4) with natalizumab can overcome this resistance. Br J Haematol. 2011;155(1):53–64. doi: 10.1111/j.1365-2141.2011.08794.x.
  46. Papayannopoulou T, Scadden DT. Stem-cell ecology and stem cells in motion. Blood. 2008;111(8):3923–30. doi: 10.1182/blood-2007-08-078147.
  47. Saito Y, Uchida N, Tanaka S, et al. Induction of cell cycle entry eliminates human leukemia stem cells in s a mouse model of AML. Nat Biotechnol. 2010;28(3):275–80. doi: 10.1038/nbt.1607.
  48. Вартанян Н.Л., Бессмельцев С.С., Семенова Н.Ю., Ругаль В.И. Мезенхимальные стромальные клетки при апластической анемии, гемобластозах и негематологических опухолях. Бюллетень СО РАМН. 2014;34(6):17–26.
    [Vartanyan NL, Bessmel’tsev SS, Rugal’ VI, Semenova NYu. Mesenchymal stromal cells in aplastic anemia, hematological malignancies and non-hematological tumors. Byulleten’ SO RAMN. 2014;34(6):17–26. (In Russ)]
  49. Raaijmakers M, Mukherjee S, Guo SH, et al. Bone progenitor dysfunction induces myelodysplasia and leukemia. Nature. 2010;464(7290):852–7. doi: 10.1038/nature08851.
  50. Герасимова Л.П., Дризе Н.И., Лубкова О.Н. и др. Нарушение стромального микроокружения у больных с различными заболеваниями системы крови. Гематология и трансфузиология. 2008;53(5):59–62.
    [Gerasimova LP, Drize NI, Lybkova ON, et al. Stromal microenvironment impairment in patients with various hematological diseases. Gematologiya i transfuziologiya. 2008;53(5):59–62. (In Russ)]

 

Biology of Hematopoietic Stem Cell Niche

REVIEWS , , ,

N.Yu. Semenova, S.S. Bessmel’tsev, V.I. Rugal’

Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: S.S. Bessmel’tsev, DSci, Professor, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel: +7(812)717-67-80; e-mail: bsshem@hotmail.com

For citation: Semenova N.Yu., Bessmel’tsev S.S., Rugal’ V.I. Biology of Hematopoietic Stem Cell Niche. Klin. Onkogematol. 2014; 7(4): 501–510 (In Russ.).

ABSTRACT

The article presents up-to-date data on the role of bone marrow stromal niche in hematopoietic stem cells regulation (HSC). It describes stages of development of the hematopoietic niche concept. Characteristics of stromal cellular elements which form the niche are presented. Mechanisms of HSC regulation by the stromal niche are reported. The role of the niche in HSC leukemic transformation is discussed. It also presents data on structural changes in the niche in case of HSC development disorder.

Keywords: hematopoietic stem cell, bone marrow, hematopoietic stem cell niche, microenvironment.

Accepted: September 1, 2014

Read in PDF (RUS)pdficon

REFERENCES

  1. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978; 4: 7–25.
  2. Пальцев М.А., Терских В.В., Васильев А.В. Что есть стволовая клетка. В кн.: Биология стволовых клеток и клеточные технологии. Под ред. М.А. Паль цева. Т. 1. М.: Медицина, Шико, 2009: 13–31. [Pal’tsev M.A., Terskikh V.V., Vasil’ev A.V. What is stem cell? In: Pal’tsev M.A., ed. Biologiya stvolovykh kletok i kletochnye tekhnologii. (Biology of stem cells and cell technologies.) Vol. 1. Moscow: Meditsina Publ., Shiko Publ.; 2009. pp. 13–31. (In Russ.)]
  3. O’Malley D.P., Kim Y.S., Perkins S.L. et al. Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders. Mod. Pathol. 2005; 18: 1550–61.
  4. Weiss L. A. Scanning electron microscopic study of the spleen. Blood. 1974; 43: 665–91.
  5. Kricun M.E. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol. 1985; 14: 10–9.
  6. Williams W., Nelson D.A. Examination of the marrow. In: Hematology Williams. Ed. by E. Beulter, M.A. Lichtman et al. New York: McGraw-Hill, 1995: 15–22.
  7. Bradford G.B., Williams B., Rossi R., Bertoncello I. Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp. Hematol. 1997; 25: 445–53.
  8. Lichtman M.A. The ultrastructure of the hemopoietic environment of the marrow: a review. Exp. Hematol. 1981; 9: 391–410.
  9. Trentin J.J. Determination of bone marrow stem cell differentiation by stromal hemopoietic inductive microenvironments (HIM). Am. J. Pathol. 1971; 65: 621–8.
  10. Wolf N.S., Trentin J.J. Hemopoietic colony studies: V. Effect of hemopoietic organ stroma on differentiation of pluripotent stem cells. J. Exp. Med. 1968; 127: 205–14.
  11. Avecilla S.T., Hattori K., Heissig B. et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat. Med. 2004; 10: 64–71.
  12. Tokoyoda K., Egawa T., Sugiyama T. et al. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004; 20: 707–18.
  13. Dexter T.M., Allen T.D., Lajtha et al. Stimulation of differentiation and proliferation of haemopoietic cells in vitro. J. Cell Physiol. 1973; 82: 461–73.
  14. Dexter T.M., Allen T.D., Lajtha L.G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J. Cell Physiol. 1977; 91: 335–44.
  15. Cheshier S.H., Morrison S.J., Liao X., Weissman I.L. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc. Natl. Acad. Sci. USA. 1999; 96: 3120–5.
  16. Calvi L.M., Adams G.B., Weibrecht K.W. et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425: 841–46.
  17. Zhang J., Niu C., Ye L. et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003; 425: 836–41.
  18. Kiel M.J., Yilmaz O.H., Iwashita T. et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121: 1109–21.
  19. Nagasawa T., Omatsu Y., Sugiyama T. Control of hematopoietic stem cells by the bone marrow stromal niche: the role of reticular cells. Trends Immunol. 2011; 32(7): 315–20.
  20. Martin T.J., Sims N.A. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol. Med. 2005; 11: 76–81.
  21. Lian J.B., Stein G.S., Aubin J.E. Bone formation: maturation and functional activities of osteoblast lineage cells. In: Primer on the metabolic bone diseases and disorders of mineral metabolism. Ed. by M.J. Favus. Washington, DC: American Society for Bone and Mineral Research, 2003: 13–28.
  22. Adams G.B., Martin R.P., Alley I.R. et al. Therapeutic targeting of a stem cell niche. Nat. Biotechnol. 2007; 25: 238–43.
  23. Taichman R.S., Emerson S.G. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J. Exp. Med. 1994; 179: 1677–82.
  24. Taichman R.S., Reilly M.J., Emerson S.G. Human osteoblasts support human hematopoietic progenitor cells in vitro bone marrow cultures. Blood. 1996; 87: 518–24.
  25. Taichman R.S., Emerson S.G. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells. 1998; 16: 7–15.
  26. Taichman R.S., Reilly M.J., Emerson S.G. The hematopoietic microenvironment: osteoblasts and the hematopoietic microenvironment. Hematology. 2000; 4: 421–6.
  27. Visnjic D., Kalajzic Z., Rowe D.W. et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004; 103: 3258–64.
  28. Kiel M.J., Radice G.L., Morrison S.J. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. Stem Cell. 2007; 1: 204–17.
  29. Arai F., Hirao A., Ohmura M. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004; 118: 149–61.
  30. Wilson A., Murphy M.J., Oskarsson T. et al. C-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev. 2004; 18: 2747–63.
  31. Yoshihara H., Arai F., Hosokawa K. et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. 2007; 1: 685–97.
  32. Fleming H.E., Janzen V., Lo Celso C. et al. Wnt-signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell. 2008; 2: 274–83.
  33. Nilsson S.K., Johnston H.M., Whitty G.A. et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood. 2005; 106: 1232–9.
  34. Stier S., Ko Y., Forkert R. et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J. Exp. Med. 2005; 201: 1781–91.
  35. Adams G.B., Chabner K.T., Alley I.R. et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature. 2006; 439: 599–603.
  36. Yin T., Li L. The stem cell niches in bone. J. Clin. Invest. 2006; 116: 1195–201.
  37. Broxmeyer H.E., Orschell C.M., Clapp D.W. et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J. Exp. Med. 2005; 201: 1307–18.
  38. Papayannopoulou T., Scadden D.T. Stem-cell ecology and stem cells in motion. Blood. 2008; 111: 3923–30.
  39. Sugiyama T., Kohara H., Noda M., Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006; 25: 977–88.
  40. Sipkins D.A., Wei X., Wu J.W. et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005; 435: 969–73.
  41. Ругаль В.И., Семенова Н.Ю. Морфология синусоидальных сосудов гемопоэтической ниши костного мозга. В кн.: Актуальные вопросы меди- цинских морфологических дисциплин. Коллективная монография под ред. В.П. Волкова. Новосибирск: СибАК, 2014: 62–80. [Rugal’ V.I., Semenova N.Yu. Morphology of sinousoid vessels of the bonemarrow hematopoietic-stem-cell niche. In: Volkov V.P., ed. Aktual’nye voprosy meditsinskikh morfologicheskikh distsiplin. (Urgent problems of medical morphological disciplines.) Novosibirsk: SibAK Publ.; 2014. pp. 62–80. (In Russ.)]
  42. Rafii 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: 3353–63.
  43. Li W., Johnson S.A., Shelley W.C., Yoder M.C. Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells. Exp. Hematol. 2004; 32: 1226–37.
  44. Cumano A., Godin I. Ontogeny of the hematopoietic system. Ann. Rev. Immunol. 2007; 25: 745–85.
  45. Orkin S.H., Zon L.I. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008; 132: 631–44.
  46. Orkin S.H., Zon L.I. SnapShot: hematopoiesis. Cell. 2008; 132: 712.
  47. de Saint-Georges L., Miller S.C. The microcirculation of bone and marrow in the diaphysis of the rat hemopoietic long bones. Anat. Rec. 1992; 233: 169–77.
  48. Narayan K., Juneja S., Garcia C. Effects of 5-fluorouracil or total-body irradiation on murine bone marrow microvasculature. Exp. Hematol. 1994; 22: 142–8.
  49. Brandi M.L., Collin-Osdoby P. Vascular biology and the skeleton. J. Bone Miner. Res. 2006; 21: 183–92.
  50. Maes C., Carmeliet P., Moermans K. et al. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Mech. Dev. 2002; 111: 61–73.
  51. Maes C., Kobayashi T., Kronenberg H.M. A novel transgenic mouse model to study the osteoblast lineage in vivo. Ann. N.Y. Acad. Sci. 2007; 1116: 149–64.
  52. Haug J.S., He X.C., Grindley J.C. et al. N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells. Cell Stem Cell. 2008; 2: 367–79.
  53. Wilson A., Oser G.M., Jaworski M. et al. Dormant and self-renewing hematopoietic stem cells and their niches. Ann. N.Y. Acad. Sci. 2007; 1106: 64–75.
  54. Morrison S.J., Wright D.E., Weissman I.L. Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization. Proc. Natl. Acad. Sci. USA. 1997; 94: 1908–13.
  55. Randall T.D., Weissman I.L. Phenotypic and functional changes induced at the clonal level in hematopoietic stem cells after 5-fluorouracil treatment. Blood. 1997; 89: 3596–606.
  56. Zhang J., Li L. Stem cell niche: microenvironment and beyond. J. Biol. Chem. 2008; 283: 9499–503.
  57. Baron R. General Principles of Bone Biology. In: Primer on the metabolic bone diseases and disorders of mineral metabolism. Ed. by M.J. Favus. Washington, DC: American Society for Bone and Mineral Research, 2003: 1–8.
  58. Belloni P.N., Tressler R.J. Microvascular endothelial cell heterogeneity: interactions with leukocytes and tumor cells. Cancer Metastas. Rev. 1990; 8: 353–89.
  59. Afan A.M., Broome C.S., Nicholls S.E. et al. Bone marrow innervation regulates cellular retention in the murine haemopoietic system. Br. J. Haematol. 1997; 98: 569–77.
  60. Katayama Y., Battista M., Kao W.M. et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006; 124: 407–21.
  61. Mendez-Ferrer S., Lucas D., Battista M., Frenette P.S. Haematopoietic stem cell release is regulated by circadian oscillations. Nature. 2008; 452: 442–7.
  62. Calvo W., Forteza-Vila J. On the development of bone marrow innervation in new-born rats as studied with silver impregnation and electron microscopy. Am. J. Anat. 1969; 126: 355–71.
  63. Calvo W., Forteza-Vila J. Schwann cells of the bone marrow. Blood. 1970; 36: 180–8.
  64. Yamazaki K., Allen T.D. Ultrastructural morphometric study of efferent nerve terminals on murine bone marrow stromal cells, and the recognition of a novel anatomical unit: the «neuro-reticular complex». Am. J. Anat. 1990; 187: 261–76.
  65. Spiegel A., Shivtiel S., Kalinkovich A. et al. Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling. Nat. Immunol. 2007; 8: 1123–31.
  66. Jacenko O., Roberts D.W., Campbell M.R. et al. Linking hematopoiesis to endochondral skeletogenesis through analysis of mice transgenic for collagen X. Am. J. Pathol. 2002; 160: 2019–34.
  67. Walkley C.R., Olsen G.H., Dworkin S. et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell. 2007; 129: 1097–110.
  68. Walkley C.R., Shea J.M., Sims N.A. et al. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell. 2007; 129: 1081–95.
  69. Iwata M., Awaya N., Graf L. et al. Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells. Blood. 2004; 103: 4496–502.
  70. Li L., Milner L.A., Deng Y. et al. The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity. 1998; 8: 43–55.
  71. Kollet O., Dar A., Shivtiel S. et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat. Med. 2006; 12: 657–64.
  72. Fukuhara S., Sako K., Minami T. et al. Differential function of Tie2 at cellcell contacts and cell-substratum contacts regulated by angiopoietin-1. Nat. Cell Biol. 2008; 10: 513–26.
  73. Saharinen P., Eklund L., Miettinen J. et al. Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat. Cell Biol. 2008; 10: 527–37.
  74. Ferrara N., Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr. Rev. 1997; 18: 4–25.
  75. Zelzer E., Olsen B.R. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr. Top. Dev. Biol. 2005; 65: 169–87.
  76. Sacchetti B., Funari A., Michienzi S. et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007; 131: 324–36.
  77. Shi S., Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J. Bone Miner Res. 2003; 18: 696–704.
  78. Duhrsen U., Hossfeld D.K. Stromal abnormalities in neoplastic bone marrow diseases. Ann. Hematol. 1996; 73: 53–70.
  79. Бессмельцев С.С. Множественная миелома (патогенез, клиника, диагностика, дифференциальный диагноз). Часть 1. Клин. онкогематол. 2013; 6(3): 237–58. [Bessmel’tsev S.S. Multiple myeloma (pathogenesis, clinical features, diagnosis, differential diagnosis). Part 1. Klin. Onkogematol. 2013; 6(3): 237–58. (In Russ.)]
  80. Semenova N., Bessmeltsev S., Rugal V. Nicheforming stromal elements of bone marrow and lymph nodes in CLL. Haematologica. 2014; 99(s1): 743.
  81. Ругаль В.И., Бессмельцев С.С., Семенова Н.Ю. и др. Структурные особенности паренхимы и стромы костного мозга больных множественной миеломой. Биомедицинский журнал Medline.ru. 2012; 13: 515–23. [Rugal’ V.I., Bessmel’tsev S.S., Semenova N.Yu. et al. Structural features of bone marrow parenchyma and stroma in patients with multiple myeloma. Biomeditsinskii zhurnal Medline.ru. 2012; 13: 515–23. (In Russ.)]
  82. Bessmeltsev S., Rugal V. Stromal microenvironment and stem cells niche in multiple myeloma. Haematologica. 2010; 95(25): 569–570.
  83. Kim Y.W., Koo B.K., Jeong H.W. et al. Defective Notch activation in microenvironment leads to myeloproliferative disease. Blood. 2008; 112: 4628–38.
  84. Raajimakers M.H., Mukherjee S., Guo S. et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010; 464: 852–7.
  85. Blau O., Hofmann W.K., Baldus C.D. et al. Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia. Exp. Hematol. 2007; 35: 221–9.
  86. Sala-Torra O., Hanna C., Loken M.R. et al. Evidence of donor-derived hematologic malignancies after hematopoietic stem cell transplantation. Biol. Blood Marrow Transpl. 2006; 12: 511–7.
  87. Colmone A., Amorim M., Pontier A.L. et al. Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science. 2008; 322: 1861–5.
  88. Jin L., Hope K.J., Zhai Q. et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat. Med. 2006; 12: 1167.
  89. Krause D.S., Lazarides K., von Andrian U.H., van Etten R.A. Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat. Med. 2006; 12: 1175–80.
  90. Miyake K., Underhill C.B., Lesley J., Kincade P.W. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J. Exp. Med. 1990; 172: 69–75.
  91. Katayama Y., Hidalgo A., Chang J. et al. CD44 is a physiological Eselectin ligand on neutrophils. J. Exp. Med. 2005; 201: 1183–9.
  92. Dimitroff C.J., Lee J.Y., Rafii S. et al. CD44 is a major E-selectin ligand on human hematopoietic progenitor cells. J. Cell Biol. 2001; 153: 1277–86.
  93. Krause D.S., von Andrian U.H., van Etten R.A. Selectins and their ligands are required for for homing and engraftment of BCR-ABL leukemia-initiating cells. Blood. 2005; 106: 106a.
  94. Jin L., Lee E.M., Ramshaw H.S. et al. Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell. 2009; 5: 31–42.
  95. Garg M., Moore H., Tobal K., Liu Yin J.A. Prognostic significance of quantitative analysis of WT1 gene transcripts by competitive reverse transcription polymerase chain reaction in acute leukaemia. Br. J. Haematol. 2003; 123: 49–59.
  96. Ishikawa F., Yoshida S., Saito Y. et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat. Biotechnol. 2007; 25: 1315–21.
  97. Saito Y., Uchida N., Tanaka S. et al. Induction of cell cycle entry eliminates human leukemia stem cells in s a mouse model of AML. Nat. Biotechnol. 2010; 28: 275–80.
  98. Klyuchnikov E., Kroger N. Sensitising leukemic cells by targeting microenvironment. Leuk. Lymphoma. 2009; 50: 319–20.
  99. Matsunaga T., Takemoto N., Sato T. et al. Interaction between leukemiccell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat. Med. 2003; 9: 1158–65.
  100. Mraz M., Zent C.S., Church A.K. et al. Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin alpha-4-beta-1 (VLA-4) with natalizumab can overcome this resistance. Br. J. Haematol. 2011; 155: 53–64.
  101. Vianello F., Villanova F., Tisato V. et al. Bone marrow mesenchymal stromal cells non-selectively protect chronic myeloid leukemia cells from imatinib-induced apoptosis via the CXCR4/CXCL12 axis. Haematologica. 2010; 95: 1081–9.
  102. Weisberg E., Azab A.K., Manley P.W. et al. Inhibition of CXCR4 in CML cells disrupts their interaction with the bone marrow microenvironment and sensitizes them to nilotinib. Leukemia. 2012; 26: 985–90.
  103. Bhatia R., McGlave P.B., Dewald G.W. et al. Abnormal function of the bone marrow microenvironment in chronic myelogenous leukemia: role of malignant stromal macrophages. Blood. 1995; 85: 3636–45.
  104. Bewry N.N., Nair R.R., Emmons M.F. et al. Stat3 contributes to resistance toward BCR-ABL inhibitors in a bone marrow microenvironment model of drug resistance. Mol. Cancer Ther. 2008; 7: 3169–75.
  105. Scupoli M.T., Perbellini O., Krampera M. et al. Interleukin 7 requirement for survival of T-cell acute lymphoblastic leukemia and human thymocytes on bone marrow stroma. Haematologica. 2007; 92: 264–6.
  106. Yamamoto-Sugitani M., Kuroda J., Ashihara E. et al. Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia. Proc. Natl. Acad. Sci. USA. 2011; 108: 17468–73.
  107. Lane S.W., Wang Y.J., Lo Celso C. et al. Differential niche and Wnt requirements during acute myeloid leukemia progression. Blood. 2011; 118: 2849–56.
  108. Wei J., Wunderlich M., Fox C. et al. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell. 2008; 13: 483–95.
  109. Spitzer T.R., Dey B.R., Chen Y.B. et al. The expanding frontier of hematopoietic cell transplantation. Cytometr. B. Clin. Cytom. 2012; 82(5): 271–9.
  110. Jordan C.T., Upchurch D., Szilvassy S.J. et al. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia. 2000; 14: 1777–84.
  111. Kugler M., Stein C., Kellner C. et al. A recombinant trispecific singlechain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting. Br. J. Haematol. 2010; 150: 574–86.
  112. Krause D.S., Fulzele K., Catic A. et al. Parathyroid hormone-induced modulation of the bone marrow microenvironment reduces leukemic stem cells in murine chronic myelogenous-leukemia-like disease via a TGFbeta-dependent pathway. Blood. 2011; 118: 1670.

Basic mechanisms of angiogenesis in hematological malignancies

REVIEWS , , ,

А.А. Vartanyan

N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

ABSTRACT

Currently, the concept of VEGF-induced angiogenesis as a growth-limiting factor for solid tumors is generally accepted. Growing evidence indicates that the angiogenic growth factors also play an important role in the development and persistence of hematological malignancies. Neoplastic cells induce angiogenesis within the bone marrow through the secretion of soluble angiogenesis activators. VEGF is thought to be a major angiogenic factor involved in bone marrow vascularization. On the other hand, the increased VEGF secretion leads to the release of several soluble cytokines such as GM-CSF, G-CSF, IL-6, PlGF, HGF, IGF, and angiopoietins by the bone marrow microenvironment cells that promote survival and proliferation of malignant cells. The increased plasma VEGF level in the patients with hematological malignancies is considered the most important prognostic factor indicating an unfavorable outcome.

In this review, we discuss the autocrine and paracrine mechanisms of VEGF accumulation in the bone marrow, as well as the angiogenesis-related and -unrelated effects of VEGF. In conclusion, the potential of VEGF signaling inhibition in various hematological malignancies for therapy and its outcomes is discussed.

Keywords: oncohematology, bone marrow, angiogenesis, antiangiogenic therapy.

Read in  PDF (RUS)pdficon

References

  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.

 

Mixed chimerism following allogeneic bone marrow transplantation: cases report

BONE MARROW TRANSPLANTATION , , , ,

K.N. Melkova, N.V. Gorbunova, T.Z. Cherniavskaya

FSBI «N.N. Blokhin Russian Cancer Research Center» RAMS, Moscow, Russian Federation

ABSTRACT

Cimerism monitoring after the bone marrow transplantation (BMT) by a method based on the quantitative polymerase chain reaction (PCR), is important for the assessment of efficiency of transplantation, early identification of recurrence and timely correction of therapy. Clinical examples of the mixed chimerism after allogeneic BMT are presented.

Keywords: allogeneic transplantation, chimerism, mixed chimerism, bone marrow, hematopoietic stem cells.

Read in PDF (RUS)pdficon

REFERENCES

  1. Appelbaum F.R., Forman S. J., Negrin R.S., Blume K.G. Thomas’ Hematopoietic Cell Transplantation, 4th ed. Malden: Blackwell Publishing Ltd., 2009: 316–27.
  2. Blum W., Brown R., Lin H.-S. et al. Low-dose (550 cGy), single-exposure total body irradiation and cyclophosphamide: Consistent, durable engraftment of related-donor peripheral blood stem cells with low treatment-related mortality and fatal organ toxicity. Biol. Blood Marrow Transplant. 2002; 8(11): 608–18.
  3. Tutschka P.J., Copelan E.A., Klein J.P. Bone Marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood 1987; 70(5): 1382–8.
  4. Munker R., Lasarus H.M., Atkinson K. The BMT Data Book, 2nd ed. Cambridge University Press, 2009: 331–56.
  5. Matutes E., Pickl W.F., van’t Veer M. et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 2011; 117: 3163–71.
  6. Румянцев А.Г., Масчан А.А. Трансплантация гемопоэтических стволовых клеток у детей. М.: МИА, 2003: 405. [Rumyantsev A.G., Maschan A.A. Transplantatsiya gemopoeticheskikh stvolovykh kletok u detei (Hematopoietic stem cell transplantation in children). M.: MIA, 2003: 405.]