靶向抑制TCTP在急性髓系白血病治疗中的作用及机制研究

项目名称： 靶向抑制TCTP在急性髓系白血病治疗中的作用及机制研究

项目编号： No.81470317

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： 童建华

作者单位： 上海交通大学

项目金额： 75万元

中文摘要： 白血病是血液系统的一种恶性疾病，在青少年恶性肿瘤中发生率占首位。长期以来，化疗一直是白血病治疗的主要手段，但这种方法缺乏特异性，毒副作用大。因此，探索白血病治疗的新途径是国内外学者的共同目标。随着维甲酸治疗急性早幼粒白血病（APL）和伊马替尼治疗慢性髓系白血病（CML）取得成功，白血病靶向治疗这一理念现已为国内外学者广泛接受。翻译控制肿瘤蛋白（TCTP）是一种在真核生物细胞中广泛存在的蛋白质，在细胞增殖凋亡和肿瘤发生发展中起重要作用。本项目拟在已有工作的基础上，从体内外不同水平探讨以靶向抑制TCTP为基础治疗急性髓系白血病（AML）的新途径，以及将TCTP作为白血病临床诊断和疗效跟踪标志的可能性。同时，通过深入研究相关的分子机制，阐明TCTP在AML发生发展中的重要作用，为临床治疗复发耐药的APL患者提供新的靶标和思路，也为实现APL以外其他AML靶向治疗的突破提供实验和理论依据。

中文关键词： 翻译控制肿瘤蛋白；靶向治疗；急性髓系白血病；细胞凋亡

英文摘要： Leukemia is a malignant disease in hematopoietic system. The occurrence of leukemia occupies the top first in adolescent malignant tumors. Traditional chemotherapy has long been the primary means of leukemia treatment. However, this approach is lack of specificity and can produce many kinds of toxic side effects. Exploration of new strategies in leukemia treatment is therefore a common goal of hematologists over the world. With the great success in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and in chronic myeloid leukemia (CML) treated with imatinib, the concept of target-based therapy for leukemia has been now widely accepted by researchers. It has been known that TCTP (translationally controlled tumor protein) is a ubiquitous protein in eukaryotic cells, which plays important roles in cell proliferation, apoptosis and tumor development. Based on our previous work, this project intends to investigate, from the different levels of in vitro and in vivo, a novel approach to treat acute myeloid leukemia (AML) by targeting inhibition of TCTP, and to evaluate the possibility of TCTP as a new biological marker of AML diagnosis and prognosis in clinic. In addition, by in-depth research on TCTP-related molecular mechanisms, we will try to clarify the roles of TCTP in the development of AML, providing new targets and new ideas for the treatment of relapsed and ATRA-resistant APL patients. Moreover, this study will furnish the experimental and theoretical basis for achieving the breakthrough in target-based therapy of AML other than APL.

英文关键词： TCTP;targeting therapy;acute myeloid leukemia;apoptosis