重新启动肿瘤细胞衰老不仅抑制肿瘤细胞在体内的发展，而且激活免疫系统清除衰老细胞的强大功能，是抗肿瘤研究的重要新策略之一。前期研究发现：PF-3758309是可以促进AML细胞衰老并具有强大抗肿瘤能力的新型小分子抑制剂；PF-3758309靶基因PAK4在促进AML逃逸细胞衰老中发挥重要作用；PAK4高表达AML患儿预后明显较差； KIF20A-GATA4 可能是PAK4促进AML逃逸细胞衰老的关键下游分子；PAK4-KIF20A-GATA4 很可能是促进AML逃逸细胞衰老的关键分子轴，以上科学发现尚未见任何文献报道。本项目拟进一步明确PAK4-KIF20A-GATA4分子轴的调控关系，揭示其调控机制，明确PAK4-KIF20A-GATA4 分子轴促进AML逃逸肿瘤细胞衰老的功能及其价值，探索该分子轴的临床意义，为AML的防治提供新的理论依据和潜在的干预靶标。

It is one of the most important strategies to study the anti-tumor effect of tumor cells by restarting the cell senescence of tumor cells which inhibiting the growth of tumor cells in the body, and activating the immune system to eliminate the aging cells. Our previous research found that PF-3758309 can promote AML cell senescence and this new small molecule inhibitors have strong anti-tumor capacity, and PF-3758309 target gene PAK4 play an important role in the regulation of escaping senescence of AML cells, high expression of PAK4 was related with poor prognosis of pediatric AML patients, further study found that KIF20A-GATA4 may be a key downstream molecular of PAK4 in escaping AML cell senescence, PAK4-KIF20A-GATA4 is likely to be a key molecule axis escaping cell senescence of AML tumor cells, these finding never been reported. This project intends to further clarify the regulation between PAK4-KIF20A-GATA4 molecular axis, to reveal regulatory mechanisms, molecular function and anti tumor of PAK4-KIF20A-GATA4 molecular axis in senescence of AML cells , to explore the clinical significance of the molecular axis, and provide a new theoretical basis and potential therapeutic targets for the prevention and treatment of AML.