DOT1L and leukemia: By targeting multiple points in the leukemic signaling network—ranging from chromatin modifications (DOT1L and chromatin remodeling complexes such as BRG1/BRM and KDM4C), transcriptional regulation (BRD4 and MYC) to the structural and functional disruption of the KMT2A fusion proteins themselves—these strategies aim to dismantle the leukemia at its core.