急性早幼粒细胞白血病细胞磷脂酰丝氨酸的细胞定位与凝血

项目名称： 急性早幼粒细胞白血病细胞磷脂酰丝氨酸的细胞定位与凝血

项目编号： No.30871227

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 史家岚

作者单位： 哈尔滨医科大学

项目金额： 31万元

中文摘要： 磷脂酰丝氨酸是细胞衰老、死亡和凝血通路上的重要信号分子。乳粘素能够通过其C2 结构域与磷脂酰丝氨酸特异结合。本项目以常合并弥漫性血管内凝血的急性早幼粒细胞白血病细胞为研究对象，采用新技术手段- -利用我们合成的Lact-C2 蛋白作为信号转导的偶联和标记的小分子探针，联合细胞转染等分子生物学方法，对正常和急性早幼粒细胞白血病细胞在进行抗肿瘤药物处理以后，诱导细胞分化和凋亡的过程中磷脂酰丝氨酸在细胞外膜和细胞内的聚合、解离、定位和活性的时空变化进行了基础研究；利用乳粘素竞争细胞膜外表面磷脂酰丝氨酸结合靶点的特点，对凝血通路进行干预，以期揭示不同作用机制的抗肿瘤药物治疗急性早幼粒细胞白血病前后磷脂酰丝氨酸的亚细胞分布的动态变化规律，阐明磷脂酰丝氨酸在该病凝血紊乱中所起的作用，寻找治疗凝血紊乱的新靶点，并对乳粘素治疗急性早幼粒细胞白血病凝血紊乱奠定理论和技术基础。

中文关键词： 磷脂酰丝氨酸；乳粘素；急性早幼粒细胞白血病；凝血；探针

英文摘要： Phosphatidylserine (PS) is an important signal molecule on the cell aging, death and blood coagulation pathway. Lactadherin can specifically bind PS through its C2 domain. Acute promyelocytic leukemia is often accompanied with disseminated intravascular coagulation. We use the new technology means including Lact-C2 protein, as a signal transduction and the coupling of small molecular marker probe, the joint cell transfer methods such as molecular biology. The basic studies on the PS aggregation, dissociation, location, and activities in and on the cell membrane, as the time and space changes, were performed on normal control mononuclear and acute promyelocytic leukemia cells with differentiation and apoptosis after treatments of anticancer drug. Lactadherin compete target binding sites of PS on cell membrane. Before and after treatments, intervention of coagulation pathway may uncover the different mechanisms of anti-tumor treatments and show the rules of the dynamic changes of PS subcellular distribution, clarify the role of PS the APL, find new targets for treatments of abnormal coagulation, and finally offer the theoretic and technical basis for the treatments of APL by lactadherin.

英文关键词： phosphatidylserine；lactadherin；acute promyelocytic leukemia；coagulation；probe