Genetic analysis of dasatinib-treated chronic myeloid leukemia rapidly developing into acute myeloid leukemia with monosomy 7 in Philadelphia-negative cells.

Nina Larsson, Rolf Billström, Henrik Lilljebjörn, Carin Lassen, Johan Richter, Marja Ekblom, Thoas Fioretos

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Abstract

Despite the recent success of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), approximately 2-17% of patients develop clonal cytogenetic changes in the Philadelphia-negative (Ph(-)) cell population. A fraction of these patients, in particular those displaying trisomy 8 or monosomy 7, are at risk of developing a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Consequently, there is a need to characterize the clinical features of such cases and to increase our understanding of the pathogenetic mechanisms underlying the emergence of clonal cytogenetic changes in Ph(-) cells. To date, most cases reported have received treatment with imatinib. Here we describe the case of a patient with CML who developed monosomy 7 in Ph(-) cells during dasatinib therapy. At 20 months after dasatinib initiation, the patient developed MDS, which rapidly progressed into AML. Genome-wide 500K SNP array analysis of the monosomy 7 clone revealed no acquired submicroscopic copy number changes. Given the strong association between monosomy 7 and mutation of genes involved in the RAS pathway in juvenile myelomonocytic leukemia, we also screened for pathogenetic variants in KRAS, NRAS, and PTPN11, but did not detect any changes.
Original languageEnglish
Pages (from-to)89-95
JournalCancer Genetics and Cytogenetics
Volume199
Issue number2
DOIs
Publication statusPublished - 2010

Subject classification (UKÄ)

  • Hematology
  • Medical Genetics
  • Cell and Molecular Biology

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