白血病的诱导分化治疗具有重要意义。申请者前期研究结果显示，大蒜中的有效成分DADS能诱导人白血病细胞分化并能增加ROS的产生，筛选DADS诱导HL-60细胞分化的差异蛋白质，发现calreticulin表达下调。基于calreticulin对肿瘤细胞的分化具有重要的调控作用，而抑制calreticulin可促进C/EBPα的表达，我们提出了DADS可通过ROS信号通路下调calreticulin并引起其移位、促进C/EBPα 的表达而诱导人白血病细胞分化的科学假说。本课题通过构建重组细胞系、SCID小鼠成瘤，应用激光共聚焦、RIP-Chip、FCM、qPCR、western blot等实验技术，体内外研究calreticulin在DADS诱导人白血病细胞分化中的作用及分子机制，深入阐明DADS诱导白血病细胞分化的作用机制，为开发白血病细胞分化的诱导剂提供理论基础和实验依据。

Developing new differentiation-induced drugs for blocking leukemia is of clinical significance. Our previous research demonstrated that the main effective component of garlic, Diallyl disulphide (DADS), induces differentiation and increases the products of ROS in leukemia cells. Through proteomic analysis, we identified differentially expressed proteins during DADS-induced differentiation in HL-60 cells, and one of them is calreticulin. Calreticulin is an important regulator of tumor cell differentiation and its down-regulation promotes C/EBPα expression. We hypothesize that DADS causes down-regulation and translocation of calreticulin through the ROS pathway and subsequently promotes expression of C/EBPα, leading to induced differentiation in leukemia cells. We will address this hypothesis using the approaches including genetically engineering cell lines, tumor formation in SCID mice, RIP-Chip, FCM, qPCR, and Western blot. The result of our proposed study will lead to a better understanding of the molecular mechanisms of DADS-induced leukemia cell differentiation and provide essential knowledge for the development of differentiation inducers to treat leukemia.