TMCC2在骨髓增殖性肿瘤中的功能和机制研究

Myeloproliferative neoplasm (MPN) is a class of malignant clonal hematonosis, the efficacy of targeting JAK2 needs improving. It’s essential to investigate the mechanism of MPN and find novel therapeutic targets. Previous studies indicate that TMCC2 promoted megakaryocyte differentiation, and was associated with ET, yet the function and mechanism of TMCC2 in MPN pathogenesis have not been reported. First, we will study the association of TMCC2 gene expression and SNP with MPN. Second, we will investigate the influence of TMCC2 on megakaryocyte proliferation and differentiation. Third, we will adopt mice bone marrow transplantation to investigate the influence of TMCC2 overexpression and TMCC2 silencing on MPL W515L induction of MPN. Fourth, at cellular and molecular level, we will investigate the mechanism how TMCC2-AKT-GATA1 axis regulates megakaryocyte proliferation and differentiation. This project attempts to clarify the function and mechanism of TMCC2 in MPN pathogenesis, in order to provide novel targets and strategies for MPN prevention and treatment.

骨髓增殖性肿瘤(MPN)是一类恶性克隆性血液病，靶向JAK2的疗效尚待提高。研究MPN的发病机制，寻找新的治疗靶点迫在眉睫。前期研究表明TMCC2促进巨核细胞分化并与ET相关，但TMCC2在MPN发生中的功能及机制尚未见报道。本项目将首先探索TMCC2基因表达及SNP与MPN的相关性。第二，研究TMCC2对巨核细胞增殖和分化的影响。第三，利用小鼠骨髓移植模型分别研究TMCC2过表达和TMCC2沉默对MPL W515L诱发MPN的影响。第四，从细胞分子水平探索TMCC2-AKT-GATA1轴调控巨核细胞增殖和分化的机制。本项目将力图阐明TMCC2在MPN发生中的功能及机制，为MPN的防治提供新靶点和新策略。

骨髓增殖性肿瘤(MPN)是一类恶性克隆性血液病，靶向JAK2的疗效尚待提高。研究MPN的发病机制，寻找新的治疗靶点迫在眉睫。前期研究表明TMCC2促进巨核细胞分化并与ET相关，但TMCC2在MPN发生中的功能及机制尚未见报道。本项目首先探索了TMCC2基因表达及SNP与MPN的相关性。第二，研究TMCC2对巨核细胞增殖和分化的影响。第三，利用小鼠骨髓移植模型分别研究TMCC2过表达和TMCC2沉默对MPL W515L诱发MPN的影响。第四，从细胞分子水平探索TMCC2-AKT-GATA1轴调控巨核细胞增殖和分化的机制。本项目发现TMCC2第1号内含子中rs1668871位点的单碱基多态性与真性血小板增多症相关。TMCC2活化细胞内多条信号通路，促进巨核细胞分化。本项目部分阐明了TMCC2在MPN发生中的功能及机制，将为MPN的防治提供新靶点和新策略。