In our study, the DOT1L protein and related H3K79 methylation were downregulated by ATM deficiency in MLLr-AML, and the cellular and molecular signatures affected by ATM deficiency resembled those caused by a lack of DOT1L; as such, we primarily considered DOT1L to be a downstream target of ATM that regulates LSC maintenance and MLLr-AML cell survival. The gene discussed is DOT1L; the disease is acute myeloid leukemia.