Finally, we showed that SUMO1 modification of PKM2 at K270 is essential in recruiting SUMO-interacting motif (SIM)-bearing Runt-related transcription factor 1(RUNX1), a master transcriptional factor implicated in the differentiation of leukemia cells, providing a molecular basis for PKM2 as a potential target which may offer synergistic effect with differentiation therapy in the treatment of leukemia. Here, PKM is linked to leukemia.