Rapid clonal shifts in response to kinase inhibitor therapy in chronic myelogenous leukemia are identified by quantitation mutation assays.
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Rapid clonal shifts in response to kinase inhibitor therapy in chronic myelogenous leukemia are identified by quantitation mutation assays.
Cancer Sci. 2010 May 22;
Authors: Yin CC, Cortes J, Galbincea J, Reddy N, Breeden M, Jabbour E, Luthra R, Jones D
Treatment of CML with the tyrosine kinase inhibitor (TKI) imatinib mesylate results in the emergence of point mutations within the kinase domain (KD) of the BCR-ABL1 fusion transcript. The introduction of next-generation TKIs that can overcome the effects of some BCR-ABL1 KD mutations requires quantitative mutation profiling methods to assess responses. We report the design and validation of such quantitative assays, using pyrosequencing and mutation-specific RT-PCR techniques, to allow sequential monitoring and illustrate their use in tracking specific KD mutations (e.g. G250E, T315I, and M351T) following changes in therapy. Pyrosequencing and mutation-specific RT-PCR allows sequential monitoring of specific mutations and identification of rapid clonal shifts in response to kinase inhibitor therapy in CML. Rapid reselection of TKI-resistant clones occurs following therapy switch in CML. (Cancer Sci 2010).
PMID: 20557306 [PubMed - as supplied by publisher]