糖代谢重塑是肿瘤细胞重要的生化特征。近几年来，本课题组聚焦糖酵解途径开展研究，报道了糖酵解限速酶丙酮酸激酶M2（PKM2）在应激时对肿瘤细胞生长的重要调控作用。最近，我们发现PKM2在体内和体外均能显著抑制白血病细胞向粒系分化，并进一步发现PKM2与分化相关转录因子RUNX1相互作用并抑制其表达。将二者相互作用的关键位点突变后，PKM2丧失了抑制粒系分化的能力。基于这些重要原创性发现，本课题拟深入研究PKM2调控白血病细胞粒系分化的代谢和非代谢机制，在绘制白血病细胞粒系分化的糖代谢图谱基础上，发现糖代谢调控和白血病细胞粒系分化之间的关联，揭示糖代谢通路参与白血病发生发展的关键机制，并为开发分化相关的白血病治疗策略提供新的分子干预靶点。

The reprogram of metabolism is an important characteristic of tumor. We recently focused on glycolysis and reported that pyruvate kinase M2(PKM2) modulates metabolism and cell growth in response to stress. More recently, we found that PKM2 inhibited myeloid differentiation of leukemic cells in vitro and in vivo. Moreover, PKM2 interacts with RUNX1 and suppressed its expression. Mutation of the key site of PKM2 which is critical in mediating the interaction between PKM2 and RUNX1 abrogated the inhibitory effect of PKM2 on myeloid differentiation. Based on these original data, we will further investigate the function and mechanism of PKM2 during myeloid differentiation of leukemia cells. Meanwhile, we will detect the level of metabolites in glucose related metabolism during myeloid differentiation of leukemic cells. This project will reveal the relationship between metabolism of glucose and differentiation and identify the key metabolic mechanism responsible for leukemogenesis and potential drug targets for differentiation-related leukemia therapy.