Fig. 2
Oncogenic mutations linking autophagy to the tumorigenesis and anticancer effects in AML. The FLT-ITD3 mutation in AML cells increases ATF4 protein-mediated basal autophagy to promote tumorigenesis. Overexpression of the enzyme sirtuin 1 is frequently observed in AML patients with FLT3-ITD mutation, although the role of sirtuin 1 in AML autophagy is unclear. A RET protein in FLT3-dependent AML inhibits autophagy via mTORC1 pathways, while the RET inhibitor suppresses leukemic cell proliferation by autophagic degradation of mutant FLT3. Also, a FLT3-ITD inhibitor induces expression of the lipid ceramide to execute lethal mitophagy. Inactivation of WWP1 induces autophagy to impair tumor growth. Inhibition of c-KITN822K blocks constitutive activation of c-KIT and induces both apoptosis and autophagy. The transcription factor TFEB induces AML differentiation and apoptosis through the IDH1/2–TET2 axis in Myc protein-deficient conditions. The mutant NPM1 gene activates leukemogenic autophagy through PML/AKT signaling, ULK1 protein stabilization, and PKM2 enzyme-mediated phosphorylation of the Beclin-1 protein. The KITD816V mutation in AML constitutively activates the STAT3 signaling pathway, enhancing basal autophagy to promote AML cell proliferation. The U2AF1S34F mutation increases autophagy flux through the Foxo3a transcription factor. AML cells with the TP53wild type gene can survive through ATG5/7 protein-mediated autophagy. The Hsp70 inhibitor, 17-AAG, under a condition of metabolic stress, induces degradation of TP53R248Q in AML through chaperone-mediated autophagy