Annexin A1(ANXA1)具有复杂的生物学功能，其在急性髓系白血病(AML)中的作用尚不清楚。我们前期研究发现ANXA1在AML患者外周血和骨髓以及AML细胞系中显著高表达，阻断ANXA1功能显著抑制AML细胞增殖，并诱导Notch1、Smad2和p15特异性高表达，提示该调控过程可能由Notch1/Smad2/p15信号轴介导。基于前期研究结果，本项目拟开展以下工作：1)扩大临床样本量，明确ANXA1与AML患者临床相关性；2)采用分子细胞学方法研究ANXA1在AML细胞增殖中的作用；3)通过鉴定ANXA1互作蛋白，信号通路干预，ANXA1表达干预、功能回复和蛋白质组学等研究初步阐明ANXA1调控AML细胞增殖的分子机制；4)在AML人源化小鼠模型中验证ANXA1调控 AML细胞增殖的作用与机制。本项目将明确ANXA1作为AML药物靶标的潜在应用价值，为临床AML治疗提供新策略。

Annexin A1 (ANXA1) has complex biological functions, while its role in acute myeloid leukemia (AML) is unclear. Our previous study identified ANXA1 was overexpressed in the peripheral blood, bone marrow and cell lines of AML patients, and demonstrated that blocking the function of ANXA1 significantly inhibited the proliferation of AML cells and up-regulated expression of Notch1, Smad2 and p15, implicating a potential Notch1/Smad2/p15 mediated ANXA1 function in AML. To fully characterize the role of ANXA1 in AML, in the present project, we therefore will determine the prognostic value of ANXA1 in AML by expanding clinical sample sizes, to investigate the functions of ANXA1 on AML cell lines, and to elucidate the molecular mechanisms underlying ANXA1 promoting AML cell proliferation through identification of ANXA1 interacting proteins, intervention of signalling pathway activity, modulation of gene expression, as well as the proteomics technique. The effects and mechanisms of ANXA1-mediated AML cells proliferation will be further examined in AML mouse models. This project will uncover ANXA1 as a potential drug target and provide novel therapeutic approaches for AML treatment.