Collectively, these results suggest that EVI1 facilitates the expression of LAPTM4B, thereby activating the mTOR signaling pathway, likely through KDM6B-mediated H3K27me3 demethylation at the promoter region of LAPTM4B in both Lin–c-Kit+ mouse BM cells and AML cells. This evidence concerns the gene MECOM and acute myeloid leukemia.