Though SETBP1 is dispensable for the development or maintenance of AML as reported, we show that up-regulation of endogenous SETBP1 with a physiologically relevant level in FLT3ITD-mutated MOLM-13 cells by CRISPR activation (but not retrovirus transduction) promote the aggressiveness of FLT3ITD AML cells via activation of FLT3/STAT5 signaling. Here, SETBP1 is linked to acute myeloid leukemia.