MLL-AF9+急性髓系白血病（AML）是一类难治性白血病，申请人已发表的工作表明组蛋白去甲基化酶JMJD3通过激活“应激/炎症髓系造血”从而促进AML细胞的分化，但JMJD3在AML免疫逃逸中的调控作用尚不清楚。通过预实验我们发现与其他AML亚类相比，在MLL-AF9+AML小鼠中体内过表达JMJD3对AML细胞的杀伤作用弱于其在体外的直接杀伤作用。体内过表达JMJD3后AML细胞免疫检查点分子PD-L1和CD155的表达上调，T细胞相应耗竭分子PD-1和TIGIT的表达上调；同时，JMJD3还激活AML细胞IFN-γ信号通路并上调MHC-II分子。据此我们设想：“JMJD3对AML的免疫逃逸具有双向调控效应，但净效应为免疫抑制”。本项目拟在MLL-AF9+AML小鼠模型、细胞系及患者骨髓标本中，深入探讨JMJD3在免疫逃逸中的调控作用及相关分子机制，为AML的免疫治疗寻找新的分子靶点。

MLL-AF9+ acute myeloid leukemia (AML) is a kind of refractory leukemia. Our published work shows that the histone demethylase JMJD3 promotes the differentiation and apoptosis of AML cells by activating "emergency/inflammatory myelopoiesis". However, compared with other AML subclasses, the killing effect of JMJD3 on MLL-AF9+ AML mouse model was much weaker in vivo than in vitro. After the overexpression of JMJD3 in MLL-AF9+ AML mouse model, the expression of immune checkpoint molecules PD-L1 and CD155 was increased in AML cells, and the expression of exhaustion molecules PD-1 and TIGIT was increased in T cells. At the same time, JMJD3 also activated IFN-γ signaling pathway and upregulated MHC-II. According to these results, we assume that JMJD3 regulates immune evasion of AML cells in a double-edged way, but the net effect is immunosuppression. We intends to explore the function of JMJD3 on immune evasion of MLL-AF9+ AML and the underlying molecular mechanism, using MLL-AF9+ AML mouse model, AML cell lines and bone marrow samples of AML patients, in search of new molecular targets for immunotherapy of AML.