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  • Title: Clonal evolution with double Ph followed by tetraploidy in imatinib-treated chronic myeloid leukemia with e19a2 transcript in transformation.
    Author: Oshikawa G, Kurosu T, Arai A, Murakami N, Miura O.
    Journal: Cancer Genet Cytogenet; 2010 May; 199(1):56-61. PubMed ID: 20417871.
    Abstract:
    Chronic myeloid leukemia (CML) with the e19a2 transcript coding for p230 is typically associated with a benign clinical course unless accompanied at presentation with additional chromosomal abnormalities. We report here a case of CML with e19a2 who did not show additional chromosomal abnormalities at diagnosis, but progressed to the fatal advanced stage in approximately 2 years. The patient was initially treated with imatinib, which, however, could be administered only intermittently at reduced doses because of recurrent thrombocytopenia and fluid retention. Nine months after starting imatinib, fluorescence in situ hybridization (FISH) with the BCR/ABL-ES fusion probe revealed 96% and 3% of bone marrow cells with one and two BCR/ABL1 fusion signals, respectively. Two years after starting therapy, leukocytosis recurred and the bone marrow contained 8.2% large and bizarre myeloblasts. Cytogenetic analysis revealed double Ph clones as well as tetraploid cells with four to five Ph chromosomes. FISH analysis confirmed the presence of cells with two to five BCR/ABL1 fusion signals. The patient died of disease progression in 2 months. No point mutation was detected in the region coding for the BCR/ABL tyrosine kinase domain by sequence analysis. It is speculated that the amplification of the BCR/ABL1 fusion gene by duplication of Ph and tetraploidy led to the progression of CML with the e19a2 transcript.
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