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Similar patterns of chromosome abnormalities in CML occur in addition to the Philadelphia chromosome with or without tyrosine kinase inhibitor treatment

Leukemia volume 24, pages 638–640 (2010)Cite this article

In chronic myeloid leukemia (CML), the progress from chronic phase (CP) to advanced disease with accelerated phase (AP) or blast phase (BP) is frequently accompanied or preceded by cytogenetic evolution within the Philadelphia-positive (Ph+) clones: although in CP additional chromosomal alterations are identified in <5% of patients only, their frequency increases to 30% in AP and up to 80% in patients with BP.1 This phenomenon is believed to reflect the genetic instability of CML.1 It was clearly shown that the additional chromosomal alterations follow nonrandom patterns:2 The ‘major route changes’ comprise alterations such as trisomy 8, isochromosome i(17q) or an extra Philadelphia chromosome. Diverse numerical abnormalities (for example, monosomy 7 or trisomy 21) and the t(3;21)(q26;q22) have been identified as ‘minor route changes.’ These specific chromosomal alterations are associated with diverse prognostic profiles: although alterations such as the t(3;21) are indicative of an adverse prognosis and rapid progression to BP, others—for example, trisomy 8—are less unfavorable. Corresponding to the pre-imatinib era, the Ph+ clonal cytogenetic evolution was still identified to worsen prognosis in patients receiving imatinib,3 although good responses to imatinib were still possible.4 In a cohort of 141 patients having received treatment with imatinib for CP following interferon failure, O'Dwyer et al.5 described a 50% relapse risk in patients with clonal evolution in contrast to 3% in those without evidence of this phenomenon.

Thus, the clinical impact of Ph+ clonal evolution in patients receiving imatinib has been investigated in several studies. However, whether the introduction of tyrosine kinase inhibitors (TKIs) has induced changes in these cytogenetic patterns, remains to be clarified, as all respective studies were performed before the introduction of imatinib.2 We here compared two subgroups: (1) 245 CML patients with evidence of Ph+ clonal evolution all investigated in the Munich Leukemia Laboratory (MLL) in the period 2005–2009 under treatment with TKIs and (2) 500 CML patients who had been published in the Mitelman Database before the year 2000 (for example, before the introduction of imatinib) (http://cgap.nci.nih.gov/Chromosomes/Mitelman).

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Authors and Affiliations

  1. MLL Munich Leukaemia Laboratory, Munich, Germany

    C Haferlach, S Schnittger, T Weiss, W Kern & T Haferlach

  2. Clinic for Stem Cell Transplantation, University Cancer Center Hamburg, Hamburg, Germany

    U Bacher

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  1. C Haferlach
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  2. U Bacher
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  3. S Schnittger
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  4. T Weiss
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  6. T Haferlach
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Correspondence to C Haferlach.

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Haferlach, C., Bacher, U., Schnittger, S. et al. Similar patterns of chromosome abnormalities in CML occur in addition to the Philadelphia chromosome with or without tyrosine kinase inhibitor treatment. Leukemia 24, 638–640 (2010). https://doi.org/10.1038/leu.2009.222

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