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Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy

Leukemia volume 21, pages 2394–2396 (2007)Cite this article

In the majority of patients with chronic myelogenous leukemia (CML), the Philadelphia chromosome (Ph+), t(9;22)(q34;q11.2), can be identified easily by conventional cytogenetic analysis of bone marrow specimens. The development of additional chromosomal abnormalities in Ph-positive metaphases, or ‘clonal evolution’, reflects the genetic instability frequently associated with advanced stages of the disease.1 Clonal evolution is a criterion for accelerated phase, has been reported in up to 80% of patients in blast phase1 and has been linked to worse outcomes in patients with CML treated with the tyrosine kinase inhibitor (TKI) imatinib mesylate.1

The presence of clonal chromosomal abnormalities in Ph-negative cells has been described occasionally in patients with CML receiving interferon-α (IFN-α),2 and is an increasingly recognized occurrence in patients treated with imatinib and other TKIs (for example, dasatinib, nilotinib and bosutinib).1, 3 These abnormalities appear in up to 15% of patients treated with imatinib, but are frequently transient and rarely associated with adverse clinical consequences. However, some reports have associated the development of these cytogenetic abnormalities with secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).4, 5 Thus far, all reports have described the development of these abnormalities in bone marrow cells. We herein report the first case of Ph-negative extramedullary (cutaneous) myeloid leukemia in a patient with CML who exhibited simultaneously clonal abnormalities of chromosomes 7 and 11 in both Ph-positive and Ph-negative cells in bone marrow. Therapy with the potent TKI nilotinib led to a response in the bone marrow and peripheral blood with a significant decrease in BCR-ABL1 transcripts, but failed to arrest the progression of cutaneous Ph-negative AML lesions.

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Authors and Affiliations

  1. Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    A Quintás-Cardama, H Kantarjian & J Cortes

  2. Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    L V Abruzzo

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  1. A Quintás-Cardama
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  2. H Kantarjian
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  3. L V Abruzzo
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  4. J Cortes
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Correspondence to A Quintás-Cardama.

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Quintás-Cardama, A., Kantarjian, H., Abruzzo, L. et al. Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy. Leukemia 21, 2394–2396 (2007). https://doi.org/10.1038/sj.leu.2404865

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