Trisomy of chromosome 8 in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia treated with inhibitors of BCR-ABL tyrosinkinases


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Abstract

Aim. To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK).
Material and methods. A total of 386 patients with CML (chronic phase - 288, acceleration phase - 77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand - investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made.
Results. The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients.
Conclusion. Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.

References

  1. Nowell P. C., Hungerford D. A. Chromosome studies on normall and leukemic human leukocytes. J. Natl. Cancer Inst. 1960; 25: 85-109.
  2. Rowley J. D. A new consistent chromosomal abnomality in chronic myelogenous leukemia giemsa starting. Nature 1973; 243: 290-303.
  3. Fialkow P. J., Jacobson R. J., Papayannopoulou T. Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. Am. J. Med. 1997; 63: 125-130.
  4. Gordon M. Y. Cellular and molecular mechanisms in chronic myeloid leukemia: biology and treatment. Br. J. Haematol. 1996; 95: 10-20.
  5. Домрачева Е. В., Захарова Е. А., Асеева Е. А. Прогностическое значение дополнительных цитогенетических аномалий при хроническом миелолейкозе. Гематол. и трансфузиол. 2005; 50 (4): 37-41.
  6. Мартынкевич И. С., Мартыненко Л. С., Иванова М. П. и др. Дополнительные хромосомные аберрации у больных хроническим миелолейкозом. Гематол. и трансфузиол. 2007; 52 (2): 28-35.
  7. Guilhot F., Chastang C., Michallet M. et al. For the French CML Study Group. Interferon alfa-2b combined with cytarabin versus interferon along in chronic myelogenous leukemia. N. Engl. J. Med. 1997; 337 (4): 223-229.
  8. Kantarjian H. M., Cortes J. E., O'Brien S. et al. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood 2003; 101: 97-100.
  9. Guilhot F. G., Roy L., Millot F. Update of first-line in chronic phase chronic myeloid leukemia. In: Hematology: Educational program of the 11 congress of EHA, Amsterdam, the Netherlands, June 15-18, 2006. Amsterdam; 2006: 93-97.
  10. O'Brien S. G., Guilhot F. G., Goldmann G. V. et al International randomized study interferon versus STI571(IRIS) 7-year follow up: sustained survival, low rate of transformation and increased rate of major molecular response (MMR) in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM). Blood 2008; 112: 76, abstr. 186.
  11. Jabbour E., Kantarjian H., Abruzzo L. Chromosomal abnomalites in Philadelphia Chromosome (Ph)-negative metaphases during novel tyrosine kinase inhibitors. Blood 2006; 108 (11): abstr. 2115, 600a.
  12. Haferlach C., Schnittger S., Fabarius A. Analysis of Philadelphia negative clones detected during treatment with tyrosine kinase inhibitors. A study on 63 CML cases. Blood 2007; ASH, abstr. 4541, 207B.
  13. Meeus P., Demuynck H., Martiat Ph. et al. Sustained, clonal karyotype abnormalities in the Philadelphia chromosome negative cells of CML patients successfully treated with Imatinib. Leukemia 2003; 17: 465-467.
  14. Deininger M. N. Chronic myeloid leukemia. Management of early stage disease. Hematol. Am. Soc Hematol., 2005: 174-182.
  15. Туркина А. Г., Хорошко Н. Д., Дружкова Г. А. и др. Эффективность терапии иматиниб мезилатом (гливеком) в хронической фазе миелолейкоза. Тер. арх. 2003; 8: 23-25.
  16. Козинец Г. И., Дульцина С. М., Герасимова Н. А., Дягилева О. А. Цитохимическая характеристика гемопоэтических клеток здоровых людей: Метод. рекомендации. М.; 1980: 33-35.
  17. Stephen G., Francois G., Richard A. et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic - phase chronic myeloid leukemia. N. Engl J. Med. 2003; 348: 994-1004.
  18. Schoch C., Haferlach T., Kernn W. et al. Occurrence of additional chromosome aberrations in chronic myeloid leukemia patients treated with imatinib mesylate. Leukemia 2003; 17: 461-463.
  19. Nguyen P., Arthur D. C., Litz C. E. et al. Fluorescence in situ hybridization (FISH) detection of trisomy 8 in myeloid cells in chronic myeloid leukemia (CML): a study of archival blood and bone marrow smears. Leukemia 1994; 8: 1654-1662.
  20. Кишева Л. П. Дизэритропоэз при лейкозах: Автореф. дис. ... канд. мед. наук. М.; 1982.
  21. Виноградова О. Ю. Изменения метаболизма железа как показателя неэффективного эритропоэза при трансфузионно-зависимых рефрактерных анемиях: Автореф. дис. ... канд. мед. наук. М.; 1999.

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