Figure 4.

The role of autophagy in epigenetic dysregulation in AML. (A) HDAC inhibitors repress autophagic flux in DS-AMKL cells exhibiting low basal autophagy levels because of MTORC1 activation, contributing to apoptotic effects of HDAC inhibition. In contrast, t(8:21) AML cells acquire resistance against HDAC inhibitors due to autophagy induction, and the combination of HDAC inhibitors with pharmacological autophagy suppression represents a promising approach to overcoming resistance of t(8:21) AML. (B) BET inhibitors enhance autophagy through the activation of the AMPK-ULK1 pathway, thus conferring drug resistance to leukemia stem cells, which can be overcome by synergistic treatment with AMPK-inhibiting agents