Since DOT1L is a highly selective regulator of the AML oncotranscriptome in several AML subtypes, such as KMT2A, MLLT10 or NUP98-rearranged AML, as well as of NPM1 mutant AML, further investigation of DOT1L inhibition with better pharmacological properties (85, 87) is warranted. This evidence concerns the gene DOT1L and acute myeloid leukemia.