Combined Effect of 2nd Generation Inhibitors on FLT3ITD Phosphorylation

Abstract

AML (acute myeloid leukemia) is an aggressive hematopoietic malignancy with multiple signaling pathways contributing to its pathogenesis. A key role in of these pathways is the FLT3 (FMS-like tyrosine kinase receptor-3). Activation of the FLT3ITD (internal tandem duplication of FLT3) leads to decreased progression and low survivability rate. Targeting the kinase activity of FLT3 with inhibitory compounds can be used as an obvious therapeutic option. The second generation inhibitors have shown enhanced FLT3 specificity and good results in targeting AML. The aim of this study is to elucidate the combined effects of these inhibitors on FLT3ITD signal transduction.