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PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene
have been associated with clinical resistance to imatinib mesylate in chronic
myeloid leukemia (CML) patients. To shed further light on the frequency,
distribution, and prognostic significance of ABL mutations, we retrospectively
analyzed a homogeneous cohort of late chronic phase CML patients who showed
primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using
denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we
screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood
samples from 40 late chronic phase CML patients homogeneously treated with
imatinib 400 mg/d, who did not reach a major cytogenetic response at 12
months.
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