Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate

摘要: Mutations of the BCR-ABL kinase domain are a common mechanism resistance to imatinib in chronic myeloid leukemia. We screened for mutations 171 patients failing therapy. Sixty-six 23 amino acids were identified 62 (36%) not responding imatinib. Phosphate-binding loop (P-loop) most frequent (n=24; 36%). By multivariate analysis, factors associated with development older age (P=0.026) prior interferon therapy (P=0.026), and accelerated phase or blast at time failure (P=0.001). After median follow-up 38 months (range, 4-68 months) from start therapy, seven non-P-loop two P-loop mutation died. clonal evolution higher percentage peripheral blood basophils worse survival failure. Mutation status had no impact on survival. When was measured started, together duration response transformation shorter In conclusion, poor outcome, suggesting that prognosis who fail is multifactorial.