我们前期研究发现CCR9在T-ALL病人CD4+白血病T细胞上异常高表达与白血病转移和耐药密切相关，但有关CCR9高表达的产生及调控机制尚不明确，国内外未见相关研究。文献报道T-ALL发病源于Notch1信号通路的异常激活，实体瘤中研究表明Notch1的异常高表达上调NFAT的表达水平，而NFAT的活化可以促进肿瘤的转移并增强其耐药性。我们新近实验结果显示：T-ALL患者白血病细胞中Notch1和NFATc2的表达水平明显高于对照组；最新文献报道NFATc2是正常T细胞中视黄酸依赖的CCR9高表达机制中必需的协同刺激分子。为明确T-ALL中CCR9高表达的产生及调控机制，本研究拟采用EMSA，ChIP，RNAi等技术，以NFAT为切入点，探讨Notch1-HES1-NFAT信号通路在CCR9高表达的产生及调控机制中的作用，寻找阻断白血病转移和耐药的新靶标，为T-ALL的治疗提供新思路。

Our previous study found that CCR9 was highly expressed in CD4+ T leukemia cells of T-ALL, which was strongly associated with metastasis and drug resistance in leukemia.However,the regulatory mechanism of high expression of CCR9 is not known. It is reported that T-ALL originates from abnormal activation of the Notch1 signaling pathway. In solid tumors, studies have shown that the high expression of Notch1 upregulated the expression of NFAT.The activation of NFAT can promote the metastasis of tumor and enhance the drug resistance. Our recent experimental results show that: the expression level of Notch1 and NFATc2 in T-ALL cells was significantly higher than that of control group; In addition,one latest study found that NFATc2 is a necessary co-stimulatory molecule in RA-dependent high expression of CCR9 in normal T cells. In this project, we will explore the mechanism of high expression of CCR9 by EMSA, ChIP and RNAi techniques. We intend to find new target markers for blocking the metastasis and drug resistance of T-ALL.Our results will provide new clues for therapy of T-ALL.