Our study demonstrates that inhibition of the PI3K/AKT/mTOR signaling pathway in HL-60 AML cells significantly upregulates key autophagy-related genes, including Beclin-1, LC3-II, ATG5, and ATG7. This core finding indicates that PI3K/AKT/mTOR inhibitors may induce autophagy in AML cells. Here, ATG5 is linked to acute myeloid leukemia.