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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

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

Summary, in 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.

Department/s

  • Division of Clinical Genetics
  • Division of Molecular Medicine and Gene Therapy
  • Stem Cell Center
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2010

Language

English

Pages

89-95

Publication/Series

Cancer Genetics and Cytogenetics

Volume

199

Issue

2

Document type

Journal article

Publisher

Elsevier

Topic

  • Hematology
  • Medical Genetics
  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0165-4608