急性髓系白血病（AML）是一种常见的血液恶性肿瘤，化疗药物阿糖胞苷等副作用明显，临床面临的难点仍是复发。因此，急需研发高效低毒的新型药物。我们前期研究证实ROS介导的Jab1/Trx1信号通路参与AML的发生发展，所以抗氧化药物具有治疗AML的潜能。预实验显示ROS水平升高会抑制免疫细胞的活性。壬二酸（AZA）无毒无害，能降低细胞内ROS水平并杀伤AML细胞，但具体机制不明。据此推测：AZA通过直接靶向ROS通路抑制AML细胞的增殖及免疫逃逸。本项目拟通过体内外实验深入探索：① AZA对AML细胞的杀伤及对化疗药物的增敏作用，分析ROS信号通路相关靶点的变化；② AZA通过调节免疫细胞的活性，遏制AML免疫逃逸途径；③ AZA对AML的疗效，检测微小残留病灶、耐药及复发等情况。本课题旨在探讨AZA靶向ROS信号通路治疗AML的作用机制，为防治AML复发提供新方法。

Acute myeloid leukemia (AML) is a malignant disorder in the hematopoietic system. Patients with AML always experience relapse after standard therapy including cytarabine. Therefore, development of novel effective therapeutic approaches with an emphasis on less cytotoxicity is of great interest. Accumulating studies suggest that ROS play a critical role in the pathobiology and relapse of AML. Moreover, elevated ROS inhibited the activity of immune cell. Thus, it is potential to treat leukemia via ROS pathways. Our preliminary data demonstrated that azelaic acid(AZA)，nontoxic and harmless, not only decreases ROS level but also inhibits the cells viability in AML. We therefore hypothesize that AZA inhibits AML through ROS pathway and tumor evasion of the immune system. We plan to further explore the effects of AZA on AML in vitro and in vivo at the following aspects: anti-leukemia activity, tumor immunology, chemo-resistance and relapse. Overall, our project will shed light on the mechanism of AZA as an anti-leukemic strategy via ROS pathways and provide favorable therapies against AML.