MAP7在正常核型急性髓系白血病中的预后意义及分子机制

项目名称： MAP7在正常核型急性髓系白血病中的预后意义及分子机制

项目编号： No.81500118

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 付林

作者单位： 北京大学

项目金额： 18万元

中文摘要： 正常核型急性髓系白血病(CN-AML)是临床上最多的急性髓系白血病(AML)，其预后异质性极强，且缺乏有效的预后标志物。前期我们利用生物信息学发现：（1）微管结合蛋白7（MAP7）在2个独立的CN-AML数据集中均为预后不良标志物；（2）MAP7和NF-κB信号通路正相关；（3）MAP7和预测能靶向它的miR-23a、miR-195负相关。本课题拟在前期工作基础上进行：（1）定量PCR检测100例CN-AML患者，进一步对MAP7在CN-AML中的临床预后意义进行验证；（2）明确MAP7对CN-AML细胞株生物学行为及小鼠成瘤作用的影响；（3）证实MAP7在CN-AML中活化NF-κB信号通路；（4）阐明miR-23a、miR-195在CN-AML中的沉默机制及其与MAP7表达增高的关系。本课题将最终明确MAP7在CN-AML中的预后意义，为进一步细化CN-AML的危险度分层奠定理论基础。

中文关键词： 微管结合蛋白7；正常核型急性髓系白血病；预后意义；分子机制

英文摘要： Normal karyotype acute myeloid leukemia (CN-AML) is the largest cytogenetic group of AML. They have strong heterogeneity, however, lack efficient prognostic biomarkers. Using bioinformatic approaches, we have found: (1) Higher expression of MAP7 is associated with poor outcomes in 2 large cohort of CN-AML patients; (2) MAP7's expression is positively correlated with NF-κB pathway; (3) MAP7's expression is negatively correlated with miR-23a and miR-195 that may target MAP7 using prediction software analysis. Based on these above findings, we aim to carry out the following studies: (1) Validating the prognostic value of MAP7 using RQ-PCR in 100 CN-AML patients; (2) Studying how MAP7 effects the biologic behaviors of CN-AML cell lines and the oncogenesis in mice models; (3) Confirming the activating effect of MAP7 for NF-κB pathway; (4) Verifying the inhibition of MAP7 expression from miR-23a and miR-195, and clarifying the epigenetically silent mechanisms of miR-23a and miR-195. Our study will confirm MAP7's significance with clinical prognosis for CN-AML, and establish the theoretical foundation for MAP7 as an indicator to the risk stratification of CN-AML.

英文关键词： MAP7;cytogenetically normal acute myeloid leukemia;prognostic significance;molecular mechanisms