In a phase-I study, treatment with EPZ5676 resulted in a significant reduction in H3K79me2 levels, while CR was only achieved in two of the 51 r/r MLL-rearranged AML patients (59), indicating that anti-DOT1L monotherapy is not sufficient to achieve clinical benefit in r/r AML patients. Here, KMT2A is linked to acute myeloid leukemia.