domain mutations identify imatinib-treated patients with CML who have BCR-ABL kinase Real-time quantitative PCR analysis can be used as a primary screen to
2012
Abstract Mutations within the BCR-ABL kinase domain in imatinib-treated chronic myeloid leukemia are the main mechanism of acquired resistance. The early detection of mutations should provide clinical benefit by allowing early intervention. Quantitative PCR results of BCR-ABL mRNA were correlated with mutation analysis in 214 imatinib-treated patients. We determined whether there was a difference in the incidence of mutations between the patients with a greater than 2-fold rise in BCR-ABL and those with stable or decreasing levels. Of the 56 patients with a greater than 2-fold rise, 34 (61%) had detectable mutations (median rise 3.0-fold, 25 th to 75 th percentiles, 2.3 to 5.2). In 31 of these 34 patients (91%), the mutation was present at the time of the rise and became detectable within 3 months in the remaining patients. Only 1 of 158 patients (0.6%) with stable or decreasing BCR-ABL levels had a detectable mutation, P <0.0001. Thus a greater than 2-fold rise identified 34 of 35 patients (97%) with a mutation. We conclude that a rise in
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