Co-expression of wild-type FLT3 attenuates the inhibitory effect of FLT3 inhibitor on FLT3 mutated leukemia cells.

ABSTRACT: FLT3 mutation is found in about 30% of acute myeloid leukemia (AML) patients and is associated with a poor prognosis. Several FLT3 inhibitors are undergoing investigation, while their clinical efficacies were lower than expected and several resistant mechanisms to FLT3 inhibitors have been demonstrated. Although most AML cells harboring FLT3 mutation co-express wild-type (Wt)-FLT3, it is not fully understood how Wt-FLT3 expression is associated with the resistance to FLT3 inhibitors. In this study, we elucidated a resistant mechanism by which FL-dependent Wt-FLT3 activation reduced inhibitory effects of FLT3 inhibitors. We demonstrated that FL-stimulation much more strongly reduced growth inhibitory effects of FLT3 inhibitors on Wt- and mutant-FLT3 co-expressing cells than sole mutant-FLT3

SUBMITTER: Chen F 

PROVIDER: S-EPMC5216920 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature