白血病是否像实体瘤一样存在活跃的有氧糖酵解代谢（Warburg效应）尚无定论。最近，本课题组发现，M2型急性髓系白血病（AML）中存在的特异染色体易位t(8; 21)产生的AML1-ETO融合蛋白抑制糖酵解途径限速酶丙酮酸激酶M2（PKM2）的表达，AML1-ETO阳性的病人骨髓细胞中PKM2水平低于健康对照组。进一步研究发现，AML1-ETO促进PKM2入核并与PKM2存在相互作用。本项目拟以这些前期工作为基础，深入研究AML1-ETO调控PKM2的分子机制及其对白血病细胞糖代谢和增殖、分化的影响，并探讨AML病人是否存在PKM2等糖酵解基因和糖代谢异常。该项目将从全新的角度认识AML1-ETO相关AML的发生机制，为探索通过干预糖代谢途径来治疗AML的策略提供新的线索，具有重要的理论和实践意义。

It remains unclear whether leukemias have a similarly increased dependence on aerobic glycolysis(Warburg effect）. We recently found that AML1-ETO fusion protein, generated from chromosomal translocation t(8;21) which specifically exists in M2 type of acute myeloid leukemia(AML), inhibited pyruvate kinase isozymes M2(PKM2）at mRNA and protein level. PKM2 expression in AML1-ETO positive M2 patients is lower than that of healthy controls.Mechanism study revealed that AML1-ETO induces PKM2 nuclear translocation and interacts with PKM2. Based on these original findings,we plan to investigate the molecular mechanism of AML1-ETO inhibiting PKM2 and its effects on leukemic cell glycolysis，proliferation and differentiation. We will also explore the potential alteration of PKM2 and glycolysis in M2 patients. These studies will shed new insights for the mechanism of AML1-ETO related AML pathogenesis and provide novel clues for glucose metabolism-targeted therapy.