上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (9): 1234-.doi: 10.3969/j.issn.1674-8115.2012.09.021

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提升转化医学理念 促进系统整合血液病学研究

陈赛娟, 赵维莅, 张小伟, 颜晓菁, 张 济, 陈 竺   

  1. 上海血液学研究所 |医学基因组学国家重点实验室, 上海 200025
  • 出版日期:2012-09-28 发布日期:2012-09-29
  • 作者简介:陈赛娟(1951—), 女, 教授, 博士, 博士生导师, 中国工程院院士, 现任中国科协副主席、上海血液学研究所所长、医学基因组学国家重点实验室主任；电子信箱: sjchen@stn.sh.cn。
  • 基金资助:

    国家重点基础研究发展计划（“九七三”计划）(2009CB825604, 2009CB825607, 2010CB529203)；国家重大科技专项(2008ZX09312-026, 2009ZX09103-431)；国家自然科学基金重点项目(30830047, 30830119)

Accelerate the translational research and promote the systems biology study on hematology

CHEN Sai-juan, ZHAO Wei-li, ZHANG Xiao-wei, YAN Xiao-jing, ZHANG Ji, CHEN Zhu   

  1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Shanghai 200025, China
  • Online:2012-09-28 Published:2012-09-29

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摘要：

白血病是严重危害人类健康的恶性肿瘤，其发病机制有待进一步阐明。科学技术日新月异，疾病机制研究不再局限于单一的角度，而是试图整合不同层次信息，着重不同部分之间的相互关系和相互作用，以期多元化地理解生物系统发生功能异常的过程。通过系统整合生物学方法，深入研究白血病的发生和发展，并在此基础上，运用转化医学的方法探索白血病的靶向治疗，对于最终攻克这一疾病具有重要的意义。上海血液学研究所通过“211工程”的建设，在急性早幼粒细胞白血病（APL）诱导分化和凋亡的靶向治疗的理论和临床研究方面获得重大突破，使APL成为第一种可治愈的急性髓细胞白血病，也是白血病基因产物靶向治疗的成功典范，这一思路正在进一步拓展至其他类型白血病。对白血病的系统整合生物学研究也获得重大发展，在国内外率先开展了白血病基因组解剖学计划，应用外显子组测序技术发现急性单核细胞白血病中DNA甲基转移酶3A（DNMT3A）基因存在高频率突变及表观遗传性改变，并与白血病临床诊断和预后密切相关；还在全基因组水平研究了APL发病机制和PML-RARα转录抑制的靶基因等。这些成果不仅深化了白血病的发病机制研究，为全国血液领域白血病分子分型以及规范化临床路径提供指导作用，更进一步深化了“转化医学研究”的理论内涵，以靶向治疗的方法挽救了国际范围内成千上万的白血病患者。

关键词: 白血病, 系统生物学, 靶向治疗

Abstract:

Leukemia is a malignancy of serious harm to human health and its pathogenesis needs to be further clarified. With the rapid development of science and technology, study on disease mechanism is no longer limited to a single point of view, but aim to integrate the different levels of information, focus on mutual relations and interactions between molecules, in order to understand the systems biological dysfunction in the disease. Thus, using systems biological methods to study in depth the leukemia development, and in this setting, applying the idea of translational medicine to explore the targeted therapy of leukemia, has an important significance for the final capture of the disease. During the construction of the “211 Project”, Shanghai Institute of Hematology has made a major breakthrough in the basic and clinical studies of differentiation and apoptosis-induced targeted therapy of acute promyelocytic leukemia (APL), making APL the first curable acute myeloid leukemia, and the successful example of leukemia gene product-based targeted therapy. This will be further extended to other types of leukemia. Also, our group has made a significant progress on leukemia systems biology research, being the first to carry out the Leukemia Genome Anatomy Project. Using exome sequencing of acute monocytic leukemia, we identify the mutations and epigenetic changes of DNA methyltransferase 3A (DNMT3A) gene, which is closely related to the clinical diagnosis and prognosis of leukemia patients. We also study at the genome-wide level the APL pathogenesis and illustrate the target genes transcriptionally repressed by PML-RARα oncoprotein. These results not only provide guidance on leukemia pathogenesis, molecular typing and standardized clinical pathway of leukemia, but also deepen the theoretical connotations of “translational medical research” and use target therapy to save thousands of leukemia patients world-wide.

Key words: leukemia, system biology, targeted therapy