复发是急性B淋巴细胞白血病（B-ALL）治疗失败的主要原因，严重影响患者长期生存。我们在前期工作中，利用人源化NOG小鼠模型鉴定出CD34+CD19+细胞为人类B-ALL的白血病启动细胞（LIC），进一步临床研究证实初诊时具有低表达CD58的LIC(CD58-LIC)的B-ALL患者复发率明显增高，预实验发现CD58-LIC中静止期细胞比例增高、CXCR4高表达，强烈提示B-ALL启动细胞可能进一步富集于CD58-LIC亚群。本研究旨在通过人源化NOG小鼠模型，鉴定CD58-LIC的B-ALL启动和自我更新能力，阐明SDF-1/CXCR4通路在CD58-LIC和白血病niche相互作用中的调控作用，即在B-ALL启动细胞和niche两个层面阐述CD58-LIC参与B-ALL复发的作用机制，并探索以阻抑高表达CXCR4的B-ALL启动细胞为治疗靶点的可行性, 为临床治疗新策略提供理论依据。

Relapse, the major cause of treatment failure in human B-lineage acute lymphoblastic leukemia (B-ALL), seriously affects the long-term survival of B-ALL patients. Leukemia initiating cells (LICs) are defined by their ability to initiate human leukemia and self-renew in immunocompromised mice. Using neonatal NOD/SCID/IL2rγnull（NOG）mouse model, we have previously reported that CD34+CD38+CD19+ cells as well as CD34+CD38-CD19+ cells are LICs in human B-ALL. Further cohort study demonstrated that B-ALL patients with low CD58 expression by CD34+CD19+ cells (CD34+CD19+CD58- phenotype, abbreviated as CD58-LIC) at diagnosis exhibited significantly higher cumulative incidence of relapse than the CD34+CD19+CD58+ group. Our preliminary data showed that an enrichment of CD58-LIC in the G0 phase of cell cycle, and a high-expressed CXCR4 in CD58-LIC, suggesting that stromal-derived factor-1(SDF-1)/CXCR4 axis in the crosstalk between LICs and BM niche may be a major determinant of relapse. Based on our previous work, this study attempts to confirm B-ALL initiating cells are further enriched in CD58-LIC.The effect of SDF-1/CXCR4 axis in B-ALL relapse and its potential mechanism will be evaluated using humanized NOG mouse model. Furthermore, we will investigate whether targeting the LICs and their niche by disrupting the SDF-1/CXCR4 axis with CXCR4 antagonist combined with chemotherapy is a novel promising strategy to prevent relapse.