三氧化二砷在TBLR1-RARα阳性急性早幼粒细胞白血病分化和凋亡中的作用及机制研究

TBLR1-RARα融合基因是本研究组发现的一个全新的RARα融合基因。临床治疗过程中，我们发现TBLR1-RARα阳性的急性早幼粒细胞白血病（APL）对砷剂（ATO）治疗敏感。本项目针对ATO在TBLR1-RARα阳性APL中的治疗作用及作用机制进行研究：1.明确ATO对TBLR1-RARα阳性APL的分化、凋亡作用。2、阐明ATO诱导TBLR1-RARα阳性APL分化、凋亡的机制，并发现其中关键分子及通路。3、揭示ATO诱导TBLR1-RARα阳性APL分化、凋亡的转录调控机制。4、阐明ATO对TBLR1-RARα阳性APL小鼠的治疗作用，并揭示其作用机制。本项目为临床制定APL治疗方案提供理论依据和实验基础。

TBLR1-RARα fusion gene was a novel RARα fusion gene discovered by our group. In the clinical treatment, we found that TBLR1-RARα positive APL was sensitive to ATO treatment. In this proposal, we will investigate the therapeutic effect and mechanism of ATO on treating TBLR1-RARα positive APL. First, the differentiation and apoptosis of ATO treated TBLR1-RARα positive APL will be verified. Second, the mechanism of differentiation and apoptosis will be illustrated, and the pivotal molecules and pathway will be found out. Third, the mechanism of transcriptional regulation of ATO treated TBLR1-RARα positive APL will be revealed. Fourth, the therapeutic effect of ATO on TBLR1-RARα positive mice will be illustrated and the mechanism will be fruther investigated. This project will provide theoretical and experimental basis for APL clinical treatment.