HES1 and acute myeloid leukemia: It has also been reported that the Hes1 protein directly binds to STAT3 and promotes STAT3 phosphorylation and activation.32 Thus, it is possible that via induction of Hes1, FLT3/ITD + AML cells could become desensitized to TKI and reduce its effect on FLT3 signaling by blocking FLT3 expression and resulting in a shift to alternative signaling pathways.