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

Author:
  • Nina Larsson
  • Rolf Billström
  • Henrik Lilljebjörn
  • Carin Lassen
  • Johan Richter
  • Marja Ekblom
  • Thoas Fioretos
Publishing year: 2010
Language: English
Pages: 89-95
Publication/Series: Cancer Genetics and Cytogenetics1979-01-01+01:002011-01-01+01:00
Volume: 199
Issue: 2
Document type: Journal article
Publisher: Elsevier

Abstract english

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.

Keywords

  • Hematology
  • Medical Genetics
  • Cell and Molecular Biology

Other

Published
  • ISSN: 0165-4608
Thoas Fioretos
E-mail: thoas.fioretos [at] med.lu.se

Principal investigator

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67

BMC C13

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