acute myeloid leukemias

Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities

BONE MARROW TRANSPLANTATION , , , ,

TL Gindina, NN Mamaev, SN Bondarenko, ES Nikolaeva, IA Petrova, OA Slesarchuk, AS Borovkova, SV Razumova, AL Alyanskii, LS Zubarovskaya, BV Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Bondarenko SN, et al. Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities. Clinical oncohematology. 2016;9(3):271-78(In Russ).

DOI: 10.21320/2500-2139-2016-9-3-271-278

ABSTRACT

Aim. To evaluate the prognostic significance of the complex karyotype including del(5q), –7, del(7q) abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. Forty-four AML patients with chromosome 5 and/or 7 abnormalities (22 women and 22 men, aged from 1.2 to 67 years, median 31.2 years) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed.

Results. Prior to allo-HSCT, the complex karyotype (with three or more chromosomal abnormalities) was observed in 19 (43 %) patients, the monosomal karyotype was in 8 (18 %) patients. Univariate analysis demonstrated that OS and EFS differed in patients from different age groups (³ 18 vs. < 18 years; p = 0.01 and p = 0.05, respectively), with different disease status at transplantation (1 remission vs. other clinical status; p = 0.1 and p = 0.008, respectively), with and without complex karyotype (СK– vs. CK+; p = 0.05 and p = 0.002, respectively), with and without monosomal karyotype (МK– vs. MK+; p = 0.009, only for EFS), and with different stem cells source (bone marrow vs. other source; p = 0.03 only for OS). Multivariate analysis confirmed that age of 18 years and more (p = 0.02 and p = 0.01, respectively), active disease at allo-HSCT (p = 0.04 and p = 0.005, respectively), complex karyotype (p = 0.04 и p = 0.0008, respectively) and stem cell source other than bone marrow (p = 0.02 only for OS) were independent predictors of OS and EFS deterioration.

Conclusion. The study demonstrates that chromosome 5 and/or 7 abnormalities as a part of the complex karyotype is high-risk factor in AML patients undergoing allo-HSCT (unlike the monosomal karyotype), that requires the special therapeutic approach.

Keywords: acute myeloid leukemias, complex karyotype, chromosome 5 and 7 abnormalities, allogeneic hematopoietic stem cell transplantation, prognosis.

Received: March 5, 2016

Accepted: April 5, 2016

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REFERENCES

  1. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74. doi: 10.1182/blood-2009-07-
  2. Breems DA, Van Putten WL, De Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26(29);4791–7. doi: 10.1200/jco.2008.16.0259.
  3. Medeiros BC, Othus M, Fang M, et al. Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. Blood. 2012;116(13):2224–8. doi: 10.1182/blood-2010-02-
  4. Fang M, Storer B, Estey E, et al. Outcome of patients with acute myeloid leukemia with monosomal karyotype who undergo hematopoietic cell transplantation. Blood. 2011;118(6):1490–4. doi: 10.1182/blood-2011-02-
  5. Lazarus HM, Litzow MR. AML cytogenetics: the complex just got simpler. Blood. 2012;120(12):2357–8. doi: 10.1182/blood-2012-08-
  6. Kayzer S, Zucknick M, Dohner K, et al. Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood. 2011;119(2):551–8. doi: 10.1182/blood-2011-07-
  7. Voutiadou G, Papaioannou G, Gaitatzi M, et al. Monosomal karyotype in acute myeloid leukemia defines a distinct subgroup within the adverse cytogenetic risk category. Cancer Genet. 2013;206(1–2):32–6. doi: 10.1016/j.cancergen.2012.10.003.
  8. Guo RJ, Atenafu EG, Craddock K, et al. Allogeneic hematopoietic cell transplantation may alleviate the negative prognostic impact of monosomal and complex karyotypes on patients with acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20(5):690–5. doi: 10.1016/j.bbmt.2014.01.027.
  9. Cornelissen JJ, Breems D, Putten WLJ, et al. Comparative analysis of the value of allogeneic hematopoietic stem-cell transplantation in acute myeloid leukemia with monosomal karyotype versus other cytogenetic risk categories. J Clin Oncol. 2012;30(17):2140–6. doi: 10.1200/jco.2011.39.6499.
  10. Hemmati P, Schuzle-Luckow A, Terwey T, et al. Cytogenetic risk grouping by the monosomal karyotype classification is superior in predicting the outcome of acute myeloid leukemia undergoing allogeneic stem cell transplantation in complete remission. Eur J Haematol. 2013;92(2):102–10. doi: 10.1111/ejh.12216.
  11. Гиндина Т.Л., Мамаев Н.Н., Бархатов И.М. и др. Сложные повреждения хромосом у больных с рецидивами острых лейкозов после аллогенной трансплантации гемопоэтических стволовых клеток. Терапевтический архив. 2012;84(8):61–6.
    [Gindina TL, Mamaev NN, Barhatov IM, et al. Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations. Terapevticheskii arkhiv. 2012;84(8):61–6. (In Russ)]
  12. Schaffer L, McGovan-Jordan J, Schmid M. ISCN. An international System for Human Cytogenetic Nomenclature. Basel: S. Karger; 2013. pp. 140.
  13. Wawrzyniak E, Wierzbowska A, Kotkowska A, et al. Different prognosis of acute myeloid leukemia harboring monosomal karyotype with total or partial monosomies determined by FISH: Retrospective PALG study. Leuk Res. 2013;37(3):293–9. doi: 10.1016/j.leukres.2012.10.022.
  14. Yoon JH, Kim HJ, Shin SH, et al. Stratification of de novo adult acute myelogenous leukemia with adverse-risk karyotype: can we overcome the worse prognosis of adverse-risk group acute myelogenous leukemia with hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(1):80–8. doi: 10.1016/j.bbmt.2013.10.015.

Diagnostic Value of C-Reactive Protein as Marker of Infections in Patients with De Novo Acute Myeloid Leukemias

INFECTIONS IN ONCOHEMATOLOGY , , , , ,

L.N. Tarasova1, S.G. Vladimirova1, V.V. Cherepanova2

1 Kirov Scientific Research Institute for Hematology and Blood Transfusion under the Federal Medico-Biological Agency of Russia, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 Municipal Hospital No. 33, 54 pr-t Lenina, Nizhny Novgorod, Russian Federation, 603122

For correspondence: Lyudmila Nikolaevna Tarasova, DSci, Professor, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(8332)67-57-00; e-mail: vlsg@mail.ru

For citation: Tarasova LN, Vladimirova SG, Cherepanova VV. Diagnostic Value of C-Reactive Protein as Marker of Infections in Patients with De Novo Acute Myeloid Leukemias. Clinical oncohematology. 2015;8(4):442–446 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-442-446

ABSTRACT

Aim. To determine diagnostically relevant C-protein levels (CRP) as an early infection marker in patients with de novo acute myeloid leukemias (AML), to evaluate the dependence of CRP concentrations on the WBC count and leukemic blast cells in the peripheral blood.

Methods. CRP was tested in 39 patients with de novo AML (17 males and 22 females) at the age of 20 to 76 years (median age is 49). AML types according to the FAB grading were as follows: М0 — 2, М1 — 4, М2 — 23, М4 — 8, and М5 — 2 patients.

Results. CRP concentrations in patients without symptoms of an infection (n = 16) were within the range from 0 to 43 mg/l (median 5.5 mg/l). The Spearman’s rank correlation coefficients between the CRP level and WBC and blast cell counts were 0.664 (p = 0.006) and 0.473 (p = 0.062), respectively. The obtained data confirm activation of CRP synthesis in case of leukemia. In patients with an infection and/or fever (n = 23), CRP levels were significantly higher than those in patients without an infection: 8–383 mg/l (median 81 mg/l). No correlation between the CRP level and WBC and blast cell counts was found. Therefore, the CRP synthesis during the onset of AML is significantly increased as a response to the infection. In groups of patients with and without infections, 95% CI were equal to 0–40 mg/l and 12–315 mg/l, respectively. Since they overlap within the range from 12 to 40 mg/l, they may be considered a «grey zone». The CRP concentrations within this range suggest infection. CRP levels lower than 12 mg/l or higher than 40 mg/l with a high degree of probability confirm either absence or presence of infectious complications, respectively.

Conclusion. Therefore, CRP is an accessible and informative marker of infection in patients with AML during the onset of the disease. Monitoring of its levels permits to start a timely antimicrobial therapy; at that, the efficacy of the therapy can be assessed based on the dynamics of this parameter.

Keywords: acute myeloid leukemias, infectious complications, acute-phase proteins, C-reactive protein, blast cells, white blood cells.

Received: April 20, 2015

Accepted: October 22, 2015

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REFERENCES

  1. Абдулкадыров К.М., Чуданова Т.В. Диагностика и лечение бактериальных и микотических инфекций у больных гемобластозами. Вестник гематологии. 2005;1(3):5–13.
    [Abdulkadyrov KM, Chudanova TV. Diagnosis and treatment of bacterial and mycotic infections in patients with hemoblastoses. Vestnik gematologii. 2005;1(3):5–13. (In Russ)]
  2. Галстян Г.М., Городецкий В.М., Шулутко Е.М. и др. Полиорганная патология при септическом шоке у больных с гемобластозами. Анестезиология и реаниматология. 2000;2:36–40.
    [Galstyan GM, Gorodetskii VM, Shulutko EM, et al. Multiple organ impairment associated with septic shock in patients with hemoblastoses. Anesteziologiya i reanimatologiya. 2000;2:36–40. (In Russ)]
  3. Черепанова В.В., Перевалова Н.Н., Тарасова Л.Н. и др. Нарушения гемостаза у больных острым миелобластным лейкозом в процессе полихимиотерапии. Гематология и трансфузиология. 2004;49(5):27–33.
    [Cherepanova VV, Perevalova NN, Tarasova LN, et al. Impairment of hemostasis in patients with acute myeloblastic leukemia during polychemotherapy. Gematologiya i transfuziologiya. 2004;49(5):27–33. (In Russ)]
  4. Паровичникова Е.Н., Савченко В.Г., Исаев В.Г. и др. Итоги многоцентрового рандомизированного исследования по лечению острых миелоидных лейкозов взрослых. Терапевтический архив. 2007;79(7):14–9.
    [Parovichnikova EN, Savchenko VG, Isaev VG, et al. Results of multicenter, randomized study to treat acute myeloid leukemia in adults. Terapevticheskii arkhiv. 2007;79(7):14–9. (In Russ)]
  5. Птушкин В.В., Багирова Н.С. Инфекционные осложнения у больных с онкогематологическими заболеваниями. В кн.: Клиническая онкогематология: руководство для врачей. Под ред. М.А. Волковой. М.: Медицина, 2001. С. 507–28.
    [Ptushkin VV, Bagirova NS. Infectious complications in patients with oncohematological malignancies. In: Volkova MA, ed. Klinicheskaya onkogematologiya: rukovodstvo dlya vrachei. (Clinical oncohematology: manual for physicians.) Moscow: Meditsina Publ.; 2001. p. 507–28. (In Russ)]
  6. Альес В.Ф., Миронов П.И., Шадчнев А.П. Этиология, эпидемиология и классификация сепсиса у детей. Анестезиология и реаниматология. 2002;1:63–6.
    [Al’es VF, Mironov PI, Shadchnev AP. Etiology, epidemiology, and classification of sepsis in children. Anesteziologiya i reanimatologiya. 2002;1:63–6. (In Russ)]
  7. Levy MN, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250–6. doi: 10.1097/01.ccm.0000050454.01978.3b.
  8. Белобородова Н.В., Попов Д.А. Диагностическая ценность некоторых маркеров инфекции в раннем послеоперационном периоде у кардиохирургических больных. Анестезиология и реаниматология. 2005;3:45–9.
    [Beloborodova NV, Popov DA. Diagnostic value of several infection markers during early postoperation period in cardiosurgical patients. Anesteziologiya i reanimatologiya. 2005;3:45–9. (In Russ)]
  9. Миронов И.П., Цыденжапов Е.Ц., Михельсон В.А. Эволюция терминологии сепсиса у детей в последнее десятилетие. Анестезиология и реаниматология. 2006;1:69–73.
    [Mironov IP, Tsydenzhapov ETs, Mikhel’son VA. Evolution of sepsis terminology in children over last decade. Anesteziologiya i reanimatologiya. 2006;1:69–73. (In Russ)]
  10. Abraham E, Matthay MF, Dinarello CA. Consensus Conference Definitions For Sepsis, Septic Shock, Acute Lung Injury And Acute Respiratory Distress Syndrome: Time For A Reevaluation. Crit Care Med. 2000;28(1):232–5. doi: 10.1097/00003246-200001000-00039.
  11. Титов В.Н., Близнюков О.П. С-реактивный белок: физико-химические свойства, методы определения и диагностическое значение. Клиническая лабораторная диагностика. 2004;4:3–9.
    [Titov VN, Bliznyukov OP. C-reactive protein: physico-chemical properties, test methods and diagnostic value. Klinicheskaya laboratornaya diagnostika. 2004;4:3–9. (In Russ)]
  12. Шепеленко А.Ф., Хацкевич В.Л., Лищенюк О.А. и др. Роль гуморальных маркеров активности воспаления в оценке адекватности стартовой антибактериальной химиотерапии внебольничной пневмонии. Военно-медицинский журнал. 2005;1:25–30.
    [Shepelenko AF, Khatskevich VL, Lishchenyuk OA, et al. Role of humoral markers of activity of inflammation in assessment of starting antibacterial chemotherapy of community-acquired pneumonia. Voenno-meditsinskii zhurnal. 2005;1:25–30. (In Russ)]
  13. Lopez JV, Rojo JM, Rodriguez OM, et al. Fever In Emergency Department: Screening For Severe Disease. Rev Clin Esp. 2008;208(3):130–4. doi: 10.1157/13115820.
  14. Тарасова Л.Н., Черепанова В.В., Мустафина Г.Н., Владимирова С.Г. С-реактивный белок как маркер инфекции у больных острым миелобластным лейкозом. Гематология и трансфузиология. 2009;54(5):27–31.
    [Tarasova LN, Cherepanova VV, Mustafina GN, Vladimirova SG. C-reactive protein as marker of infection in patients with acute myeloblast leukemia. Gematologiya i transfuziologiya. 2009;54(5):27–31. (In Russ)]
  15. Simon L, Gauvin F, Amre DK, et al. Serum procalcitinin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Bacter Dis. 2004;39:206–17. doi: 10.1086/421997.
  16. Владимирова С.Г., Тарасова Л.М., Скольская О.Ю., Черепанова В.В. С-реактивный белок как маркер тяжести инфекционного процесса у больных острым миелоидным лейкозом при нейтропении. Терапевтический архив. 2013;85(11):34–40.
    [Vladimirova SG, Tarasova LM, Skol’skaya OYu, Cherepanova VV. C-reactive protein as marker of severity of infection in patients with acute myeloid leukemia in neutropenia. Terapevticheskii arkhiv. 2013;85(11):34–40. (In Russ)]
  17. Владимирова С.Г., Тарасова Л.М., Докшина И.А., Черепанова В.В. Оценка чувствительности и специфичности метода определения С-реактивного белка при диагностике инфекционных осложнений у больных острым лимфобластным лейкозом, получающих химиотерапию. Клиническая лабораторная диагностика. 2014;59(11):17–21.
    [Vladimirova SG, Tarasova LM, Dokshina IA, Cherepanova VV. Evaluation of sensitivity and specificity of test method for C-reactive protein in diagnosis of infectious complications in patients with acute lymphoblast leukemia on chemotherapy. Klinicheskaya laboratornaya diagnostika. 2014;59(11):17–21. (In Russ)]
  18. Антонов В.Г., Козлов В.К. Патогенез онкологических заболеваний: иммунные и биохимические феномены и механизмы. Внеклеточные и клеточные механизмы общей иммунодепрессии и иммунной резистентности. Цитокины и воспаление. 2004;3(1):8–19.
    [Antonov VG, Kozlov VK. Pathogenesis on oncological diseases: immune and biological phenomena and mechanisms. Extracellular and cellular mechanisms of general immunosuppression and immune resistance. Tsitokiny i vospalenie. 2004;3(1):8–19. (In Russ)]
  19. Kwaan HC. Double hazard of thrombophilia and bleeding in leukemia. Hematol ASH Educ Book. 2007;1:151–7. doi: 10.1182/asheducation-2007.1.151.
  20. Галстян Г.М., Берковский А.Л., Зуева А.В. и др. Фактор некроза опухоли, интерлейкин-6, эндотоксин и прокальцитонин при септическом шоке у больных с опухолевыми заболеваниями системы крови. Терапевтический архив. 2002;74(7):56–61.
    [Galstyan GM, Berkovskii AL, Zueva AV, et al. Tumor necrosis factor, interleukin-6, endotoxin, and procalcitonin in septic shock in patients with hematological malignancies. Terapevticheskii arkhiv. 2002;74(7):56–61. (In Russ)]
  21. Carrigan SD, Scott G, Tabrizian M. Toward resolving the challenges of sepsis diagnosis. Clin Chem. 2004;50(8):1301–14. doi: 10.1373/clinchem.2004.032144.
  22. Косякова Н.И., Прохоренко С.В., Прохоренко И.Р. Дисбаланс продукции цитокинов у больных тяжелым хирургическим сепсисом. Иммунология. 2005;5:319–21.
    [Kosyakova NI, Prokhorenko SV, Prokhorenko IR. Disbalance of cytokine production in patients with severe surgical sepsis. Immunologiya. 2005;5:319–21. (In Russ)]
  23. Козлов В.К. Дисфункция иммунной системы в патогенезе сепсиса: возможности диагностики. Цитокины и воспаление. 2006;5(2):15–28.
    [Kozlov VK. Immune system dysfunction in pathogenesis of sepsis: possibilities of diagnosis. Tsitokiny i vospalenie. 2006;5(2):15–28. (In Russ)]
  24. ГОСТ Р 53022. Технологии лабораторные клинические. Требования к качеству клинических лабораторных исследований. Часть 3. Правила оценки клинической информативности лабораторных тестов. М., 2008.
    [GOST Р 53022. Clinical laboratory technologies. Requirements to quality of clinical laboratory investigations. Part 3. Guidelines for evaluation of clinical information value of lab tests. Moscow; 2008. (In Russ)]
  25. Клясова Г.А. Антимикробная терапия. В кн.: Программное лечение заболеваний системы крови: сборник алгоритмов диагностики и протоколов лечения заболеваний системы крови. Под ред. В.Г. Савченко. М.: Практика, 2012. С. 829–53.
    [Klyasova GA. Antimicrobial therapy. In: Savchenko VG, ed. Programmnoe lechenie zabolevanii sistemy krovi: sbornik algoritmov diagnostiki i protokolov lecheniya zabolevanii sistemy krovi. (Program treatment of hematological diseases: collection of algorithms of diagnosing and treatment protocols of hematological diseases.) Moscow: Praktika Publ.; 2012. p. 829–53. (In Russ)]

Molecular Monitoring of WT1 Gene Expression Degree in Acute Myeloid Leukemias after Allogeneic Hematopoietic Stem Cell Transplantation

BONE MARROW TRANSPLANTATION , , , , ,

N.N. Mamaev, A.V. Gorbunova, I.M. Barkhatov, Ya.V. Gudozhnikova, T.L. Gindina, V.A. Katerina, E.V. Volchkov, A.L. Alyanskii, E.V. Babenko, O.A. Slesarchuk, N.V. Stancheva, S.N. Bondarenko, B.V. Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Nikolaevich Mamaev, DSci, Professor, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Gorbunova AV, Barkhatov IM, et al. Molecular Monitoring of WT1 Gene Expression Level in Acute Myeloid Leukemias after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2015;8(3):309–20 (In Russ).

ABSTRACT

Objective. To evaluate the possibility of serial analysis of WT1 gene expression level for prediction and diagnosis of post-transplant acute myeloid leukemia (AML) relapses.

Methods. Serial analyses of WT1 gene expression were performed using quantitative real-time PCR during the post-transplant period of 34 patients with AML. All patients underwent allogeneic hematopoietic stem cell transplantation: unrelated (n = 22), related (n = 12), including haploidentical (n = 4). 5 of 34 patients had AML transformed from the myelodysplastic syndromes (MDS). In addition, the level of donor chimerism and the bone marrow/peripheral blood blast cells counts were evaluated. AML1/ETO (n = 4) or EVI1 (n = 4) gene expression degrees were measured in 8 patients in order to compare those with the WT1 gene expression.

Results. Based on obtained data on the WT1 gene expression, two equal subgroups of patients were formed. The first one consisted of patients with stable normal expression of the investigated molecular indicator during the post-transplant period, whereas the second group consisted of patients with impaired expression. The initial level of WT1 gene expression almost did not depend on both cytological and cytogenetic AML subtypes. During the post-transplant period, the WT1 gene expression degree correlated with that of AML1/ETO or EVI1. Increased WT1 gene expression take the lead over the decreased donor chimerism and blast cell count increase in bone marrow and blood typical for post-transplant relapses of AML.

Conclusion. The higher level of WT1 gene expression may serve not only as a marker for timely diagnosis of post-transplant relapses in AML patients, but also as a monitoring parameter for testing their treatment quality.

Keywords: acute myeloid leukemias, hematopoietic stem cell transplantation, WT1 gene expression monitoring, AML1/ETO and EVI1, diagnosis of post-transplant relapses, molecular monitoring of treatment.

Received: March 19, 2015

Accepted: June 1, 2015

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REFERENCES

  1. Wertheim GB, Bagg A. Minimal residual disease testing to predict relapse following transplant for AML and high-grade myelodysplastic syndromes. Exp Rev Mol Diagn. 2011;11(4):361–6. doi: 10.1586/erm.11.19.
  2. Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;361(11):1058–66. doi: 10.1056/nejmoa0903840.
  3. Rocquain J, Carbuccia N, Trouplin V, et al. Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. BMC Cancer. 2010;10(1):401. doi: 10.1186/1471-2407-10-401.
  4. Cilloni D, Gottardi E, De Micheli D, et al. Quantitative assessment of WT1 expression by real time quantitative PCR may be a useful tool for monitoring residual disease in acute leukemia patients. Leukemia. 2002;16(10):2115–21. doi: 10.1038/sj.leu.2402675.
  5. Cilloni D, Gottardi E, Messa F, et al. WT1 as a universal marker for minimal residual disease detection and quantification in myeloid leukemias and in myelodysplastic syndrome. Acta Hematol. 2004;112(1−2):79–84. doi: 10.1159/000077562.
  6. Cilloni D, Renneville A, Hermitte F, et al. Real-time quantitative PCR (RQ-PCR) detection of minimal residual disease (MRD) by optimized WT1 assay to enhance risk stratification in acute myeloid leukemia (AML): A European LeukemiaNet Study. J Clin Oncol. 2009;27(31):5195–201. doi: 10.1200/jco.2009.22.4865.
  7. Nomdedeu JF, Hoyos M, Carricondo M, et al. Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML. Leukemia. 2013;27(11):2157–64. doi: 10.1038/leu.2013.111.
  8. Yoon JH, Kim HJ, Shin SH, et al. BAALC and WT1 expressions from diagnosis to hematopoietic stem cell transplantation: consecutive monitoring in adult patients with core-binding-factor-positive AML. Eur J Haematol. 2013;91(2):112–21. doi: 10.1111/ejh.12142.
  9. Tamaki H, Ogawa H, Inoue K, et al. Increased expression of the Wilms tumor gene (WT1) at relapse in acute leukemia. Blood. 1996;88(11):4396–8.
  10. Ogawa H, Tamaki H, Ikegame K, et al. The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia. Blood. 2003;101(5):1698–704. doi: 10.1182/blood-2002-06-1831.
  11. Bader P, Niemeyer C, Weber G, et al. WT1 gene expression: useful marker for minimal residual disease in childhood myelodysplastic syndromes and juvenile myelomonocytic leukemia? Eur J Haematol. 2004;73(1):25–8. doi: 10.1111/j.1600-0609.2004.00260.x.
  12. Lange T, Hubmann M, Burkhard R, et al. Monitoring of WT1 expression in PB and CD34+ donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning. Leukemia. 2011;25(3):498–505. doi: 10.1038/leu.2010.283.
  13. Ueda Y, Mizutani C, Nannya Y, et al. Clinical evaluation of WT1 mRNA expression levels in peripheral blood and bone marrow in patients with myelodysplastic syndromes. Leuk Lymphoma. 2013;54(7):1450–8. doi: 10.3109/10428194.2012.745074.
  14. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Аллогенная трансплантация гемопоэтических стволовых клеток при миелодиспластических синдромах и клиническое значение гиперэкспрессии гена WT1. Клиническая онкогематология. 2014;7(4):551–63.
    [Mamayev NN, Gorbunova AV, Gindina TL, et al. Allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and clinical significance of WT1 gene overexpression. Klinicheskaya onkogematologiya. 2014;7(4):551–63. (In Russ)]
  15. Heesch S, Goekbuget N, Stroux A, et al. Prognostic implications and expression of the Wilms tumor 1 (WT1) gene in adult T-lymphoblastic leukemia. Haematologica. 2010;95(6):942–9. doi: 10.3324/haematol.2009.016386.
  16. Ujj Z, Buglyo G, Udvardy M, et al. WT1 overexpression affecting clinical outcome in non-Hodgkin lymphomas and adult acute lymphoblastic leukemia. Pathol Oncol Res. 2014;20(3):565–70. doi: 10.1007/s12253-013-9729-7.
  17. Drakos E, Rassidakis GZ, Tsioli F, et al. Differential expression of WT1 gene product in non-Hodgkin lymphomas. Appl Immunohistochem Mol Morphol. 2005;13(2):132–7. doi: 10.1097/01.pai.0000143786.62974.66.
  18. Inoue K, Sugiyama H, Ogawa H, et al. WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. Blood. 1994;84(9):3071–9.
  19. Inoue K, Ogawa H, Yamagami T, et al. Long–term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels. Blood. 1996;88:2267–78.
  20. Inoue K, Ogawa H, Sonoda Y, et al. Aberrant overexpression of the Wilms’ tumor gene (WT1) in human leukemia. Blood. 1997;89(4):1405–12.
  21. Candoni A, Toffoleti E, Gallina R, et al. Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia. Clin Transplant. 2011;25(2):308–16. doi: 10.1111/j.1399-0012.2010.01251.x.
  22. Kwon M, Martinez-Laperche C, Infante M, et al. Evaluation of minimal residual disease by real-time quantitative PCR of Wilms’ Tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell transplantation: Correlation with flow cytometry and chimerism. Biol Blood Marrow Transplant. 2012;18(8):1235–42. doi: 10.1016/j.bbmt.2012.01.012.
  23. Polak J, Hajkova H, Haskovec C, et al. Quantitative monitoring of WT1 expression in peripheral blood before and after allogeneic stem cell transplantation for acute myeloid leukemia – a useful tool for early detection of minimal residual disease. Neoplasma. 2013;60(1):74–82. doi: 10.4149/neo_2013_011.
  24. Frairia C, Aydin S, Riera L, et al. WT1 expression in аcute myeloid leukaemia: a useful marker for improving therapy response evaluation. Blood. 2013;122(21): Abstract 2588.
  25. Alonso-Dominiquez JM, Tenorio M, Velasco D, et al. Correlation of WT1 expression with the burden of total and residual leukemic blasts in bone marrow samples of acute myeloid leukemia patients. Cancer Genet. 2012;205(4):190–1. doi: 10.1016/j.cancergen.2012.02.008.
  26. Zhao XS, Yan CH, Liu DH, et al. Combined use of WT1 and flow cytometry monitoring can promote sensitivity of predicting relapse after allogeneic HSCT without affecting specificity. Ann Hematol. 2013;92(8):1111–9. doi: 10.1007/s00277-013-1733-1.
  27. Yoon J-H, Kim H-J, Kim J-W, et al. Identification of molecular and cytogenetic risk factors for unfavorable core-binding factor-positive adult AML with post remission treatment outcome analysis including transplantation. Bone Marrow Transplant. 2014;49(12);1466−74. doi: 101038/bmt.2014.180.
  28. Hosen N, Shirakata T, Nishida S, et al. The Wilm’s tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis. Leukemia. 2007;21(8):1783–91. doi: 10.1038/sj.leu.2404752.
  29. Huff V. Wilm’s tumours about tumour suppressor genes, an oncogene and chameleon gene. Nat Rev Cancer. 2011;11(2):111–21. doi: 10.1038/nrc3002.
  30. Zhang Q, Zhang Q, Li Q, et al. Monitoring of WT1 and its target gene IRF8 expression in acute myeloid leukemia and their significance. Int J Lab Hematol. 2014;37(4):e67–e71. doi: 10.1111/ijlh.12309.
  31. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Трансплантация гемопоэтических стволовых клеток при остром миелоидном лейкозе с транслокацией t(8;21)(q22;q22). Клиническая онкогематология. 2013;6(4):439–44.
    [Mamayev NN, Gorbunova AV, Gindina TL, et al. Hematopoietic stem cell transplantation in AML patients with t(8;21)(q22;q22) translocation. Klinicheskaya onkogematologiya. 2013;6(4):439–44. (In Russ)]
  32. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Стойкое восстановление донорского гемопоэза у больной с посттрансплантационным рецидивом острого миеломонобластного лейкоза с inv(3)(q21q26), моносомией 7 и экспрессией онкогена EVI1 после трансфузий донорских лимфоцитов и использования гипометилирующих агентов. Клиническая онкогематология. 2014;7(1):71–5.
    [Mamayev NN, Gorbunova AV, Gindina TL, et al. Stable donor hematopoiesis recovery after post-transplantation relapse of acute myeloid leukemia in patient with inv(3)(q21q26), monosomy 7 and EVI1 oncogene overexpression after donor lymphocyte infusions and administration of hypomethylating agents. Klinicheskaya onkogematologiya. 2014;7(1):71–5. (In Russ)]
  33. Messina C, Candoni A, Carraba MG, et al. Wilms’ tumor gene 1 transcript levels in leukopheresis on peripheral blood hematopoietic cells predict relapse risk in patients autografted for acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20(10):1–6. doi: 10.1016/j.bbmt.2014.06.017.