生理、病理条件下细胞均有异质性，疾病状态下细胞异质性研究是近年前沿热点领域。白血病微环境在白血病发展中发挥重要作用，其中细胞异质性的形成和作用机制急待阐明。巨噬细胞是造血微环境的重要成员，生理条件下有显著异质性，尚无白血病中异质性机制及与白血病进展关系相关研究。在国家自然科学基金资助下，我们在国际上首次提出了白血病相关巨噬细胞（LAM）的概念并系统研究了其数量变化和表型特点，发现LAM有三方面异质性。在此基础上，本课题利用小鼠急性白血病模型，从来源异质性、组织微环境特异性活化机制异质性以及活化表型异质性三方面阐明LAM异质性机制及与白血病发展的关系，并探索针对LAM异质性进行干预的抗白血病手段，更完整地阐明白血病微环境在白血病发展中的作用和意义，完善微环境因素对肿瘤、白血病作用机制，具有重要理论意义；同时，为进一步寻找白血病治疗的新策略和靶点提供线索，具有潜在应用前景。

Cell heterogeneity is observed under both physiological and pathological conditions. In recent years, studies on cell heterogeneity in diseases are hot frontier aspects. The leukemic microenvironment play important roles in the development of leukemia. The development and mechanism of cell heterogeneity in leukemia need to be established. Macrophages, distinguished by their heterogeneity under physiological conditions, are important member in hematopoietic microenvironment. However, the mechanism of their heterogeneity and the association with the development of leukemia have not been established. During the study for the previous NSFC grants, we first proposed the criteria of leukemia-associated macrophage (LAM) in the literature and systematically studied the distribution and activation phenotypic characteristics of LAM during the development of leukemia. We observed that LAM exhibited heterogeneity in three aspects. In the present study, we will study the mechanisms of LAM heterogeneity in three aspects, i.e. heterogeneity in LAM origin, heterogeneity in tissue microenvironment-specific activation mechanisms and heterogeneity in LAM activation phenotypes. We will also study the roles of heterogenous LAM populations on the development of leukemia and explore anti-leukemia methods by intervention of LAM based on their heterogeneity. This study will not only enable us to further understand the role and significance of leukemic microenvironment on the development of leukemia, as well as the mechanism of microenvironmental factors on tumors and leukemia, but also provide clues for further study searching for new strategies and targets for the treatment of leukemia.