DOT1L, the sole identified H3K79 methyltransferase, has been targeted for cancer treatment, especially in acute leukemias with MLL gene rearrangements.1348 Pinometostat, the first clinical inhibitor of DOT1L, exhibits improved potency, longer plasma half-life, enhanced selectivity, and efficacy in reducing leukemic cell proliferation. The gene discussed is DOT1L; the disease is acute leukemia.