In this study, we reported that LAMP5-AS1 is necessary for cell self-renewal in MLL leukemia in view of its capacity to enhance the methyltransferase activity of DOT1L, which facilitates H3K79me2 and H3K79me3 modifications on the locus of the HOXA genes to upregulate their expression. The gene discussed is DOT1L; the disease is leukemia.