Given that the alternative activation of FLT3 downstream signaling like STATs, mTOR, and MAPK was an important mechanism of sorafenib resistance, we hypothesized that concomitant tumor suppressors or myeloid transcription factors mutations in FLT3-ITD AML drove sorafenib resistance via activating FLT3 downstream signaling. The gene discussed is FLT3; the disease is acute myeloid leukemia.