AML blasts with IDH1 mutations generate 2-HG, leading to hypermethylation. ATRA selectively impaired viability and induced apoptosis in these cells. Cell-permeable 2-HG sensitized wild-type AML cells to ATRA-induced differentiation. In vivo, ATRA reduced tumor burden and prolonged survival in mice bearing mutant IDH1 AML. This evidence concerns the gene IDH1 and neoplasm.