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Simultaneous occurrence of a t(9;22) (Ph) with a t(2;11) in a patient with CML and emergence of a new clone with the t(2;11) alone after imatinib mesylate treatment

Leukemia volume 17, pages 807–810 (2003)Cite this article

TO THE EDITOR

Chronic myeloid leukemia (CML) is characterized by the translocation t(9;22), called Philadelphia (Ph) chromosome. It is an acquired abnormality of hematopoietic stem cells, which is present in all dividing granulocytic, erythroid, and megakaryocytic cells in the marrow and also in some B and probably a minority of T lymphocytes. Fusion of the ABL gene on 9q34 to the BCR gene on 22q11 results in a constitutive activation of the ABL tyrosine kinase, which plays a major role in leukemogenesis.1 Although a multistep model for the development of CML has been proposed with the acquisition of the Ph chromosome as a second event,2,3,4 the expression of Bcr/Abl as a sole oncogenic event in mice results in the development of leukemia, establishing Bcr/Abl as the molecular pathogenic event in CML.5,6 The tyrosine kinase activity of the fusion protein is critical for the transforming ability, making it an attractive target for antitumor drug development. The novel molecular, targeted anticancer agent imatinib mesylate, also called STI571 or Glivec (Novartis), specifically inhibits the p210BCR/ABL tyrosine kinase activity, the in vitro growth of BCR/ABL positive cells, and eradicates Bcr/Abl positive tumors in nude mice.7,8 Phase I and II clinical trials of patients with chronic phase CML produced encouraging results with a complete hematologic response in a large proportion of patients (for a recent review, see Capdeville et al8).

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References

  1. Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock Z, Kantarjian HM . The biology of chronic myeloid leukemia. N Engl J Med 1999; 341: 164–172.

    Article  CAS  Google Scholar 

  2. Fialkow PJ, Martin PJ, Najfeld V, Penfold GK, Jacobson RJ, Hansen JA . Evidence for a multistep pathogenesis of chronic myelogenous leukemia. Blood 1981; 58: 158–163.

    CAS  PubMed  Google Scholar 

  3. Raskind WH, Ferraris AM, Najfeld V, Jacobson RJ, Moohr JW, Fialkow PJ . Further evidence for the existence of a clonal Ph-negative stage in some cases of Ph-positive chronic myelocytic leukemia. Leukemia 1993; 7: 1163–1167.

    CAS  PubMed  Google Scholar 

  4. Kaye FJ, Najfeld V, Singer J, Cuttner J, Fialkow PJ . Confirming evidence for the clonal development and stem cell origin of Philadelphia chromosome-negative chronic myelogenous leukemia. Am J Hematol 1984; 17: 93–96.

    Article  CAS  Google Scholar 

  5. Daley GQ, Van Etten RA, Baltimore D . Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990; 247: 824–830.

    Article  CAS  Google Scholar 

  6. Kelliher MA, Mc Laughlin J, Witte ON, Rosenberg N . Induction of a chronic myelogenous leukemia like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci USA 1990; 87: 6649–6653.

    Article  CAS  Google Scholar 

  7. Buchdunger E, Zimmermann J, Mett H, Meyer T, Muller M, Druker BJ et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 1996; 56: 100–104.

    CAS  Google Scholar 

  8. Capdeville R, Buchdunger E, Zimmermann J, Matter A . Glivex (STI571, Imatinib), a rationally developed, targeted anticancer drug. Nat Rev 2002; 1: 493–502.

    CAS  Google Scholar 

  9. Fleischman EW, Reshmi S, Frenkel MA . MLL is involved in a t(2;11)(p21;q23) in a patient with acute myeloblastic leukemia. Genes Chromosomes Cancer 1999; 24: 151–155.

    Article  CAS  Google Scholar 

  10. de la Chapelle A, Knuutila S, Elonen, E . Translocation (2;11)(p21;q23) in acute non-lymphocytic leukaemia: a non-random association. Scand J Haematol 1986; 45 (Suppl): 91–97.

    CAS  Google Scholar 

  11. Braziel RM, Launder TM, Druker BJ, Olson SB, Magenis R, 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 

  12. 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: 1390–1395.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Human Genetics and Anthropology, Heinrich Heine University of Duesseldorf, Duesseldorf, Germany

    B Royer-Pokora, B Hildebrandt, A Redmann, M Drechsler & C Wieland

  2. Clinic for Hematology, Oncology and Clinical Immunology, Heinrich Heine University of Duesseldorf, Duesseldorf, Germany

    C Herold, R Kronenwett & R Haas

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Royer-Pokora, B., Hildebrandt, B., Redmann, A. et al. Simultaneous occurrence of a t(9;22) (Ph) with a t(2;11) in a patient with CML and emergence of a new clone with the t(2;11) alone after imatinib mesylate treatment. Leukemia 17, 807–810 (2003). https://doi.org/10.1038/sj.leu.2402877

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