白血病的浸润和转移是威胁患者生命的主要因素之一，其发生发展与所处的微环境密切相关。目前有关NHE1与趋化性细胞因子CCL25及其受体CCR9在T-ALL微环境中的研究在国内外尚未见报道。NHE1是一种跨膜离子交换蛋白，是肿瘤微环境中的重要分子,通过调节细胞内外pH值、与细胞骨架蛋白ERM相互作用，促进细胞的迁移和侵袭。我们前期研究报道CCL25与CCR9相互作用通过活化ERM，促进了T-ALL白血病细胞的迁移，与白血病的浸润和转移密切相关。为了明确NHE1在T-ALL微环境中的作用及其分子机制,本研究拟以NHE1为切入点，以T-ALL细胞系及临床标本为研究对象，运用流式、RT-PCR、Transwell等技术探讨NHE1与CCL25/CCR9的关系，以期阐明NHE1在T-ALL微环境中的作用及其机制，为治疗白血病提供一种新思路。

Leukemic infiltration and metastasis are the main pathological factors that threaten the lives of many leukemia patients today. Its development and tumor microenvironment factors such as cytokines and others are closely related. NHE1 is a kind of transmembrane ion-protein that plays a significant role in the tumor microenvironment by regulating intracellular and extracellular pH values and interacting with the cytoskeletal proteins ERM to regulate cell migration and invasion. At present, there are little or no reports that have explored the potential interaction between NHE1 and CCL25 with its receptor CCR9 in the leukemia microenvironment. In our previous studies, we found that the interaction between CCL25 and CCR9 enhances the migration of cells by activation of the ERM in T-ALL. In order to clarify the mechanism of NHE1 in the T-ALL microenvironment, we intend to explore the relationship between NHE1 and CCL25/CCR9 by FCM, RT-PCR, Transwell technology in T-ALL cell line and T-ALL clinical samples. Our research will therefor shed light on the role of NHE1 in T-ALL microenvironment and provide new clues in the treatment of leukemia.

急性T淋巴细胞白血病（T-ALL）是威胁人类健康的血液系统恶性肿瘤。当前，转移和化疗药物耐药是T-ALL患者死亡的主要原因。Na+/H+交换器1（NHE1）在多种癌症的转移和耐药中发挥重要作用，但其在T-ALL中的作用尚不清楚。实验室前期结果表明，C型趋化性细胞因子25（CCL25）在MOLT4细胞的转移和耐药中起重要作用，并且Ezrin参与此过程。本项目中我们以MOLT4细胞为研究对象，通过Transwell和扫描电子显微镜技术探索NHE1在T-ALL转移中的作用。同时，通过激光共聚焦显微镜技术检测NHE1和Ezrin之间的关系。并通过CCK8测定检测了NHE1对MOLT4细胞多柔比星（DOX）抗性的影响。实验结果表明，CCL25处理MOLT4细胞后NHE1的表达水平上调并伴随着细胞形态的变化和NHE1与Ezrin的共定位。与此同时，与野生型MOLT4细胞相比，CCL25诱导NHE1或Ezrin沉默MOLT4细胞发生极化的能力下降。并且，NHE1或Ezrin沉默的MOLT4细胞对DOX表现出更高的敏感性。综上所述，NHE1高表达可能是T-ALL病人不良预后的潜在指标。