Fig. 2.

Illustration shows that leukemic cells design mechanisms against a variety of therapies and ultimately achieve chemotherapy-resistance through autophagy: 1—Chemotherapy increases reactive oxygen species (ROS) and induces autophagy through HIF/ BNIP3/BCL-2 signaling pathway. 2—Binding of SDF-1α as a drug to CXCR-4 activates SIRT-1 and SIRT-1 by deacetylation of ATG7, ATG5, LC3 induces autophagy. 3—Ara-C modulates AKT and ERK signaling pathways and induces mTOR-dependent autophagy. 4—By activating ATF4, it directly induces autophagy and inhibits mitophagy by inhibiting CerS1. 5—S1P production as a result of increased ceramidase acid in AML cells activates NF-κB and increases P-gp expression as a channel that causes drug efflux