CML患者TKIs治疗后部分可成功停药，目前机制不清。有研究表明可能与记忆性NK抗LSC有关。达沙替尼可通过多途径调节免疫功能，包括影响免疫细胞的PD-1的表达。我们前期研究发现达沙替尼治疗Ph+ALL伴随CMV-DNA+的患者出现NKG2C+NK的扩增，这种记忆性NK细胞对Ph+白血病株有杀伤。基于此我们提出假说: CMV启动NKG2C+记忆性NK增殖，达沙替尼下调PD1+NKG2C+NK亚群的PD1表达，增强NKG2C+NK的扩增和对LSC的杀伤。本研究拟体外达沙替尼干预CMV激活的NKG2C+NK不同亚群，探讨达沙替尼对NKG2C+NK不同亚群的影响及机理, 和NKG2C+NK不同亚群对LSC杀伤，并在CML小鼠模型验证。本研究对揭示TKIs治疗后成功停药的机制，对制定CML治疗策略有十分重要的科学意义和实用价值，对Ph+ALL治疗策略也有借鉴意义。

Some patients with CML can withdraw from TKIs after treatment, and the mechanism might be related to the effect of memory NK cells on anti-Ph+ leukemic stem cells (LSCs). Dasatinib affects immune through several pathways including the expression of PD1 in immune cells. Our previous work showed increased NKG2C+ NK cells were found in cases with CMV-DNA+ who suffered Ph+ leukemia and received Dasatinib, and these memory NK cells have anti-LSCs activity. We hypothesize that: CMV infection activates NKG2C+ memory NK cells proliferation; Dasatinib down-regulates the expression of PD1 in PD1+NKG2C+ NK cell subsets and then enhances anti-LSCs activity of these cells. In this study, the effect of Dasatinib on CMV-activated NKG2C+ cell subsets and its mechanism will be studies. Besides, the different NKG2C+ cell subsets on LSCs will be compared. The results will be verified in mouse model with CML LSC. This study might be helpful to clarify the mechanism of TKI withdrawal and to offer foundation for CMV and Ph+ ALL treatment strategies.