PMAIP1 and acute myeloid leukemia: It is currently believed that the synergistic effect of Venetoclax and HMAs may be through several mechanisms: (1) HMAs induce the expression of the pro-apoptotic protein NOXA through the integrated stress response pathway, which enhances the activation of Venetoclax-induced apoptosis in AML cells [47]; (2) Venetoclax can enhance the sensitivity of AML cells to HMAs by inhibiting the antioxidant response pathway induced by HMAs [48]; (3) Ven-HMAs together impair the tricarboxylic acid cycle of leukemic stem cells (LSCs) and deplete ATP of LSCs leading to AML cell death [49].