白血病干细胞是急性髓系白血病生长与复发的主要根源，但目前我们对其生物学特性知之甚少。因此，分离鉴定特异表达于白血病干细胞的关键分子具有重要的理论意义和应用价值。我们的前期研究首次发现急性髓系白血病干细胞高表达免疫抑制分子 CD272，其高表达与患者预后、生存率呈负相关，阻断其与配体的交联可有效抑制小鼠肿瘤的生长。这一现象目前国内外未见报道，提示白血病干细胞特异表达 CD272可能与白血病干细胞存活相关。为此，本项目拟在较大样本、不同亚型急性髓系白血病中进一步分析急性髓系白血病干细胞 CD272的表达与临床特征和机体免疫状态的相关性，从原代细胞、在体模型两方面阐述 CD272表达对白血病细胞存活及抗白血病免疫的影响并探索其机制，同时尝试以 CD272单抗实现靶向抑制，从而达到识别白血病干细胞的关键特异表面分子、为合理设计靶向白血病干细胞的治疗提供新的理论基础等目的。

Leukemia stem cell (LSC) is the primary cause of growth and recurrence, but little is known about their biological characteristics. Therefore，it is critical to isolate a molecule that is expressed or functions specifically at the AML LSCs stage. Our findings firstly showed that the immunosuppressive molecule, CD272, was highly expressed on AML LSCs. The expression of CD272 was negatively correlated with the prognosis of patients.And what's more, the growth of mouse tumor was inhibited by 6A6 through preventing HVEM and BTLA interactions. The phenomenon was first reported in AML LSCs. The results above strongly suggested that the specifical expression of CD272 on the AML LSC stage may be a new mechanism for tumor immune evasion, and may be closely related to LSC survival. The present project intends to further explore the CD272 expression on AML LSC in larger samples and different subtypes of AML, to define the correlations among the CD272 expression on AML LSC and tumor immune micro-environment and clinical features, to clarify the effect of CD272 expression on AML LSC upon the anti-leukemia immune response and LSC survival both in vitro and in vivo experiments, to make an attempt at target on AML LSCs by anti-CD272 monoclonal antibody, to identify an ideal surface molecule to target AML LSCs with sufficient specificity and sensitivity, and to provide the noval theoretical basis for the rational design of LSC-targeted therapies.