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Clonal chromosomal abnormalities in the Philadelphia chromosome negative cells of chronic myeloid leukemia patients treated with imatinib

Leukemia volume 18, pages 1140–1142 (2004)Cite this article

TO THE EDITOR

Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) is a myeloproliferative disorder, characterized by the t(9;22)(q34;q11) translocation, originating in a multipotent hematopoietic stem cell. Imatinib mesylate is a tyrosine kinase inhibitor that has been shown to block growth and induce apoptosis in BCR-ABL-expressing hematopoietic cells.1 It can also inhibit the activity of other tyrosine kinases including KIT and platelet-derived growth factor receptor (PDGFR).2 Most of the patients under imatinib achieve a major or complete cytogenetic remission (less than 35% of Ph+ metaphases in the bone marrow), with restoration of a Philadelphia-negative hematopoiesis.3 However, almost one-third of the patients have thrombocytopenia and neutropenia as a consequence of their treatment.3 Recently, some reports on the emergence of clonal chromosomal abnormalities in the Ph-negative cells of CML patients under imatinib treatment have appeared in the literature.4,5,6,7,8,9,10,11,12

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References

  1. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S et al. Effects of selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996; 2: 561–566.

    Article  CAS  Google Scholar 

  2. Capdeville R, Buchdunger E, Zimmerman J, Matter A . Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 2002; 1: 493–502.

    Article  CAS  Google Scholar 

  3. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C et al. for the International STI571 CML Study Group Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–652.

    Article  CAS  Google Scholar 

  4. Schoch C, Haferlach T, Kern W, Schnittger S, Berger U, Hehlmann R et al. Occurrence of additional chromosome aberrations in chronic myeloid leukemia patients treated with imatinib mesylate. Leukemia 2003; 17: 461–463.

    Article  CAS  Google Scholar 

  5. O'Dwyer ME, Gatter KM, Loriaux M, Druker BJ, Olson SB, Magenis RE et al. Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate. Leukemia 2003; 17: 481–487.

    Article  CAS  Google Scholar 

  6. Meeus P, Demuynck H, Martiat P, Michaux L, Wouters E, Hagemeijer A . Sustained, clonal karyotype abnormalities in the Philadelphia chromosome negative cells of CML patients successfully treated with imatinib. Leukemia 2003; 17: 465–467.

    Article  CAS  Google Scholar 

  7. Marktel S, Marin D, Foot N, Szydlo R, Bua M, Karadimitris A et al. Chronic myeloid leukemia in chronic phase responding to imatinib: the occurrence of additional cytogenetic abnormalities predicts disease progression. Haematologica 2003; 88: 260–267.

    CAS  PubMed  Google Scholar 

  8. Braziel RM, Launder TM, Druker BJ, Olson SB, Magenis RE, Mauro MJ et al. Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients: 14 months' experience. Blood 2002; 100: 435–441.

    Article  CAS  Google Scholar 

  9. Andersen MK, Pedersen-Bjergaard J, Kjeldsen L, Dufva IH, Brondum-Nielsen K . Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8. Leukemia 2002; 16: 1390–1393.

    Article  CAS  Google Scholar 

  10. Feldman E, Najfeld V, Schuster M, Roboz G, Chadburn A, Silver RT . The emergence of Ph−, trisomy-8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate. Exp Hematol 2003; 31: 702–707.

    Article  CAS  Google Scholar 

  11. Bumm T, Muller C, Al-Ali HK, Krohn K, Shepherd P, Schmidt E et al. Emergence of clonal cytogenetic abnormalities in Ph-negative cells in some CML patients in cytogenetic remission to Imatinib but restoration of polyclonal hematopoiesis in the majority. Blood 2003; 101: 1941–1949.

    Article  CAS  Google Scholar 

  12. Gozzetti A, Tozzuoli D, Crupi R, Gentili S, Bocchia M, Raspadori D et al. Emergence of Ph negative clones in chronic myeloid leukemia (CML) patients in complete cytogenetic remission after therapy with imatinib mesylate. Eur J Haematol 2003; 71: 313–314.

    Article  Google Scholar 

  13. Morel F, Ka C, Le Bris MJ, Herry A, Morice P, Bourquard P et al. Deletion of the 5'abl region in Philadelphia-positive chronic myeloid leukemia: frequency, origin and prognosis. Leukemia Lymphoma 2003; 44: 1333–1338.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Service de Cytogénétique, Cytologie et Biologie de la Reproduction, CHU Morvan, Brest, France

    N Guilbert-Douet, F Morel, M-J Le Bris & M D Braekeleer

  2. Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale, Brest, France

    N Guilbert-Douet, F Morel, C Berthou & M D Braekeleer

  3. Service d'Hématologie Clinique, CHU Morvan, Brest, France

    C Berthou

  4. Service d'Hématologie, CH La Beauchée, St-Brieuc, France

    P Morice & P Bourquard

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  1. N Guilbert-Douet
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Correspondence to M D Braekeleer.

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Guilbert-Douet, N., Morel, F., Bris, MJ. et al. Clonal chromosomal abnormalities in the Philadelphia chromosome negative cells of chronic myeloid leukemia patients treated with imatinib. Leukemia 18, 1140–1142 (2004). https://doi.org/10.1038/sj.leu.2403361

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  • DOI: https://doi.org/10.1038/sj.leu.2403361

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