Based on the urgent need to identify better and safer treatment options for leukemias driven by a rearrangement of the KMT2A gene, we report on a novel, clinically applicable combination of anti-cancer drugs, the curaxin CBL0137 and the HDAC inhibitor panobinostat, that displays significant efficacy in aggressive animal models of KMT2A-r leukemia. Here, KMT2A is linked to cancer.