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

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.

• Författare: Nina Larsson; Rolf Billström; Henrik Lilljebjörn; Carin Lassen; Johan Richter; Marja Ekblom; Thoas Fioretos
• Avdelning/ar: Avdelningen för klinisk genetik; Avdelningen för molekylärmedicin och genterapi; Stamcellscentrum (SCC); StemTherapy: National Initiative on Stem Cells for Regenerative Therapy; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publiceringsår: 2010
• Språk: Engelska
• Sidor: 89-95
• Publikation/Tidskrift/Serie: Cancer Genetics and Cytogenetics
• Volym: 199
• Issue: 2
• Fulltext: - 1 MB; Download statistics
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/20471511?dopt=Abstract; http://dx.doi.org/10.1016/j.cancergencyto.2010.02.005
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Hematology; Medical Genetics; Cell and Molecular Biology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0165-4608