The Bcr-Abl mutations T315I and Y253H do not confer a growth advantage in the absence of imatinib

摘要: Mutations in the Bcr-Abl kinase domain are a frequent cause of imatinib resistance patients with advanced CML or Ph+ ALL. The impact these mutations on overall oncogenic potential and clinical course disease absence is presently unclear. In this study, we analyzed effects P-loop mutation Y253H highly resistant T315I activity vitro transforming efficiency vivo. Immunoprecipitated Bcr-AblY253H Bcr-AblT315I proteins displayed similar activities substrate phosphorylation patterns as wildtype. We directly compared proliferative capacity mutant to wildtype primary BM cells murine transplantation model by using competitive repopulation assay. results implicate that imatinib, there no growth advantage for carrying Bcr-Ablwt, whereas treatment clearly selects leukemic expressing both Thus, analysed mutants confer resistance, but do not induce imatinib.