慢性淋巴细胞白血病NF-KappaB信号通路乙酰化修饰及其靶点治疗价值研究

项目名称： 慢性淋巴细胞白血病NF-KappaB信号通路乙酰化修饰及其靶点治疗价值研究

项目编号： No.81470329

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 缪扣荣

作者单位： 南京医科大学

项目金额： 70万元

中文摘要： 慢性淋巴细胞白血病(CLL)是一种B淋巴细胞克隆增殖性疾病，部分CLL患者伴有p53基因异常，化疗敏感性差，迫切需要探讨新的治疗策略。转录因子NF-κB由于具有致瘤性而得到研究人员的广泛关注，成为研究热点。然而其在CLL中的组蛋白乙酰化修饰作用环节及机制并未证实，更没有深入探讨其作为耐药治疗的靶点价值。本课题拟在既往国家自然科学基金课题（编号：81000216）基础上，进一步探索CLL细胞NF-κB各成员/调节物表达情况；揭示表观遗传学组蛋白修饰（乙酰化/去乙酰化）在CLL细胞NF-κB信号通路中的作用；筛选并鉴定调控基因、位点及下游靶基因情况；体外/体内实验鉴定分子干预组蛋白修饰NF-κB信号通路在CLL患者中作为氟达拉滨耐药/p53基因异常患者治疗的潜在价值，结合临床及生物学特征探讨与药物干预治疗的相关因素，进而为推动难治CLL治疗方法的改进及肿瘤的分子靶向治疗提供理论依据。

中文关键词： 慢性淋巴细胞白血病；信号通路；耐药

英文摘要： Chronic lymphocytic leukemia (CLL)is a kind of B cell clonal malignance diseases, and some CLL patients who have p53 gene mutations or deletions were resistant to common chemotherapy, which indicates that more new and effective strategies should be raised. NF-κB signal pathway has absorbed great interest of research fellow and been very hot for its role in the development of tumor.However, the mechanism of histone acetylation/deacetylation and its target genes are not still clear, nor the value for molecular target therapy in resistance CLL patients.Based on the previous NSFC (No.81000216) project, the expression of members and modulars in NF-κB pathway will be focused; the mechanism of histone acetylation/deacetylation and the target genes will be discovered; molecular target therapeytic value in chemotherapy resistance/p53 gene abnormal CLL, by in vitro and in vivo experiments，will also be studied. It can inprove CLL strategies for resistance/refractary patients and provide theries for molecular targeting therapy.

英文关键词： chronic lymphocytic leukemia;signal pathway;resistance