组蛋白去甲基化酶RBP2介导慢粒急变的分子网络调控机制

项目名称： 组蛋白去甲基化酶RBP2介导慢粒急变的分子网络调控机制

项目编号： No.81470318

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： 陈春燕

作者单位： 山东大学

项目金额： 80万元

中文摘要： 慢性粒细胞白血病（Chronic Myelogenous Leukemia，CML）一旦急变，病情恶化，预后不佳。解析其中的分子网络调控机制是CML急变研究领域的重要科学问题。申请者首次发现组蛋白去甲基化酶RBP2与CML急变密切相关，综合生命科学研究进展和前期研究基础，拟从组蛋白修饰、miRNA和BCR/ABL等多分子视域挖掘RBP2介导的CML急变分子网络调控机制，旨在为揭示CML急变发生机理提供新思路：（1）分子和细胞水平：解析组蛋白去甲基化酶RBP2介导CML急变的分子网络调控机制及其细胞生物学效应；（2）动物整体水平：应用RBP2基因敲除小鼠研究RBP2缺失诱发骨髓细胞恶性转化的效应；（3）人体组织水平：验证CML急变患者RBP2及其调控分子表达与疾病的关联性。通过上述研究，评估RBP2介导的分子网络调控机制在CML急变发生中的意义。

中文关键词： 组蛋白去甲基化酶；慢粒急变；RBP2；调控网络

英文摘要： Blast crisis (BP) is the final phase in the evolution of chronic myelogenous leukemia (CML), which indicates rapid progression and short survival. Exploring the underlying mechanism is of great importance and may contribute to better understanding of BP-CML.According to previous study, the applicant found for the first time that histone demethylase RBP2 was indicated as a molecular marker of BP-CML. Based on this finding, now we intend to elucidate the molecular regulatory network mediated by RBP2 in combination with histone modification, miRNA regulation, BCR/ABL and other molecules in BP-CML, thus providing a new way of thinking. Specifically, the study is aimed at (1) defining RBP2-mediated molecular regulatory network and its biological effects in BP-CML on a molecular and cellular basis; (2) defining the malignant transformation effect of RBP2 depletion on bone marrow cells using RBP2-knockout mice; (3) defining the correlation between disease performance in clinic settings and the expression of RBP2 as well as its targets in BP-CML patients. Based on those, the significance of the molecular regulatory network mediated by RBP2 in occurrence of BP-CML will be evaluated.

英文关键词： histone demethylase;CML blast crisis;RBP2;regulatory network