白血病细胞源性CCL3促进调节性T细胞迁移的机制及其在急性髓系白血病诊疗中的临床价值

白血病造血微环境（LHME）中调节性T细胞（Treg）的累积可加速白血病进展，但是LHME中Treg累积的具体机制不详。我们前期工作证明Treg向造血组织的迁移是LHME中Treg累积的一个重要来源，而靶向Treg迁移已成为肿瘤免疫治疗的新策略。我们还发现LHME中来源于白血病细胞的CCL3升高，其主要受体CCR1在Treg上高表达，且Treg接受CCL3刺激后pSTAT3上调，迁移能力明显增强；此外，急性髓系白血病（AML）患者CCL3及Treg的水平均显著升高。由此提出假说白血病细胞来源的CCL3通过促进Treg向造血组织的迁移从而加速白血病进程；同时提示CCL3及Treg可作为AML诊疗的新指标。本研究拟利用MLL-AF9的AML小鼠体内外一系列实验明确CCL3促进Treg向LHME迁移并加速白血病进程的机制，同时探究CCL3及Treg表达相关性在成人AML诊疗中的临床价值。

The accumulation of regulatory T cells (Treg) in leukemia hematopoietic microenvironment (LHME) can accelerate leukemia progression, but the mechanism of Treg accumulation in LHME is unknown. Our recent work proved that Treg migration to hematopoietic tissue is an important source of Treg accumulation in LHME, and targeting Treg migration has become a new strategy for tumor immunotherapy. We also found that the chemokine CCL3 derived from leukemia cells was highly expressed in LHME, and CCR1, the major receptor of CCL3, was highly expressed in Treg. The pSTAT3 expression of Tregs stimulated by CCL3 increased significantly, thus enhancing potential of Treg migration. In addition, CCL3 and Treg were highly expressed in patients with acute myeloid leukemia (AML). Based on these findings, we hypothesize that CCL3 derived from leukemia cells promotes Treg migration to hematopoietic tissue, thus accelerating leukemia progression. Additionally, the expressions of CCL3 and Treg could be considered as promising biomarkers for the diagnosis and treatment of AML. In this study, we will conduct a series of experiments of MLL-AF9 AML mouse model to explore the mechanism that CCL3 promotes Treg migration to LHME and accelerates leukemia progression. Furthermore, we will investigate the clinical potential of the correlation between CCL3 and Treg expression in the diagnosis and treatment of adult AML.