Due to the strong impact of DOT1L inhibition on proliferative signaling and the induction of myeloid differentiation irrespective of MLL-r, we hypothesized that treating both MLL-r and non-MLL-r AML cells with Pinometostat would induce sensitization to further treatment with the multi-kinase inhibitor Sorafenib. Here, DOT1L is linked to acute myeloid leukemia.