用砒霜「进攻」急性早幼粒细胞白血病 陈竺拿下 ASH 国际大奖

2016-12-14 13:09 来源:科学网 作者:黄辛 闻朝君
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12 月 5 日在美国圣地亚哥会议中心当地时间下午 1:30, 美国血液学会 (ASH) 颁发了本届欧尼斯特·博特勒奖, 获奖人员为来自上海交通大学附属瑞金医院上海血液学研究所的陈竺教授和巴黎圣路易医院的 Hugues de Thé教授。

今年的欧尼斯特·博特勒奖颁发给陈竺教授及 Hugues de Thé 教授是缘于他们在急性早幼粒细胞白血病 (APL) 基础和临床研究中所取得的突出成就。急性早幼粒细胞白血病曾是一种极为凶险, 死亡率很高的恶性血液疾病。

陈竺教授团队应用全反式维甲酸 (ATRA) 和三氧化二砷 (ATO) 对急性早幼粒细胞白血病进行联合靶向治疗, 使得这一疾病的五年无病生存率跃升至 90% 以上, 达到基本「治愈」标准。同时, 从分子机制上揭示了 ATRA 和砷剂是如何分别作用于急性早幼粒细胞白血病致病分子 PML/RARα, 将白血病细胞诱导分化和凋亡, 从而达到疾病治疗的目的。

这是一项真正的结合临床医学与基础生物学的研究, 是东方传统医学和西方医学结合的典范, 开启了在恶性血液疾病中转化治疗的重要篇章。

ASH 会议的新闻日报 (News Daily) 赞誉这一工作是「实验桌到临床转化医学概念的遗产和框架性成果」。

陈竺教授在接受奖牌之后的演讲中, 介绍了由中国学者引领的临床联合应用 ATRA 和砷剂治疗急性早幼粒细胞白血病患者的各个发展阶段, 不断进行概念设计创新及优化临床试验方案的进程, 强调了中医中药在白血病治疗理念和实践方面的重要启迪, 基于现代分子细胞和整体水平系统研究成果的临床应用, 以及中国和美欧等大型多中心临床研究的最新成就。

结果显示,ATRA 和砷剂联合靶向治疗在低/中危急性早幼粒细胞白血病患者中可获得 95% 以上长期无病生存, 而不需应用化疗。同时, 陈竺教授也提出, 减少急性早幼粒细胞白血病患者早期死亡率及早期识别并干预高危易复发患者, 将仍是未来任重而道远的工作。

急性早幼粒细胞白血病协同靶向治疗作为精准医学的范例, 应与建立和完善全民医保制度相结合, 把有关研究成果拓展到包括发展中国家在内的世界各国, 从而给更多患者带来福音。推广该范例中临床与基础相互转化的成功经验, 必将促进今后在其他恶性血液疾病研究领域的重大突破。

陈竺教授为中国科学院院士, 美国科学院和美国医学科学院外籍院士, 英国皇家学会外籍会员, 法国科学院外籍院士, 发展中国家科学院院士, 上海交通大学医学院教授、上海交通大学医学院附属瑞金医院终身教授。现任第十二届全国人民代表大会常务委员会副委员长, 中国农工民主党中央委员会主席以及中国红十字会会长、欧美同学会·中国留学人员联谊会会长。曾多次荣获国际血液/肿瘤大奖。

背景介绍

欧尼斯特· 博特勒演讲和奖项 (The Ernest Beutler Lecture and Prize) 是以 ASH 原主席 Ernest Beutler 名字命名的, 该奖项表彰在转化医学研究中有重大进展成就者, 在同一主题下由两部分演讲组成, 获奖者一位介绍基础科学进展, 另一个介绍临床科学或转化医学成就。

原文

Zhu Chen, MD, PhD, and Hugues de Thé, MD, PhD, to Present 2016 American Society of Hematology Ernest Beutler Lecture

Published on: August 04, 2016

(WASHINGTON, August 4, 2016) – The American Society of Hematology (ASH) will honor Zhu Chen, MD, of Shanghai Institute of Hematology and Hugues de Thé, MD, PhD, of Collège de France, with the 2016 Ernest Beutler Lecture and Prize for their significant research advances in the area of acute promyelocytic leukemia (APL).

The Ernest Beutler Lecture, named for the late Ernest Beutler, MD, past president of ASH and physician-scientist for more than 50 years, is a two-part lectureship that recognizes major translational advances related to a single topic. The award honors two individuals, one who has enabled advances in basic science and another for achievements in clinical science or translational research.

Drs. de Thé and Chen will present their lecture on Acute Promyelocytic Leukemia: A Model for Precision Medicine and Cure by Targeted Therapies at 1:30 p.m. on Monday, December 5, at the 58th ASH Annual Meeting and Exposition in San Diego. During their lecture, Dr. de Thé will review the pathogenesis of APL and the molecular basis for its response to therapy, and Dr. Chen will review the conceptual development and clinical advances in APL treatment.

Dr. de Thé, the recipient of the 2016 Ernest Beutler Lecture in Basic Science, is a Professor of Cellular and Molecular Oncology at the Collège de France and at Hôspital Saint-Louis in Paris. He currently heads an INSERM/CNRS research unit. He earned his MD at the University of Paris V and completed his residency in medical research at Residency Paris Hospitals. He also obtained his PhD from University of Paris VI at the Pasteur Institute.

After making important contributions to the understanding of retinoic acid signaling during his training, Dr. de Thé played a key role in the discovery of the PML/RARA oncoprotein, the driver of APL. His further studies of PML/RARA, including how it responds to treatment with retinoic acid and arsenic, led Dr. de Thé to discover further insights about the disease. Notably, his insights into the degradation of this oncoprotein formed the physio-pathological basis for definitive curative regimens, first established in mice and subsequently in patients. 

Beyond his basic research, Dr. de Thé has received numerous awards, including the French Legion of Honor, the Foreign Cooperation Award of the People’s Republic of China, and the José Carreras Award from the European Hematology Association. He currently serves as the President of the scientific advisory board at Bettencourt Schuller Foundation and has previously served as President of the Scientific Council of ARC as well as on the scientific advisory board for the TATA Memorial Foundation.

Dr. Chen, the recipient of the 2016 Ernest Beutler Prize for Clinical Science, is a Professor of Molecular Biology at Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine (SJTUSM, former Shanghai Second Medical College), and he is the former Health Minister of China. He received his medical training in Ruijin Hospital affiliated to SJTUSM, and completed both his PhD and postdoctoral training in Hôspital Saint-Louis, Université Paris VII.

Dr. Chen has made seminal contributions to the concept and successful paradigm of molecular target-based differentiation/apoptosis therapy of APL. He developed a novel targeted treatment strategy for newly diagnosed APL with all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), and led the first clinical trial combining ATRA, As2O3, and chemotherapy. This therapy has transformed APL from highly fatal to the first curable acute myeloid leukemia.  His basic/translational studies have consistently contributed to disease biology of APL and the mechanism of action of arsenic in treating this disease. 

Dr. Chen has published more than 300 papers in numerous journals, including Nature, Science, Nature Genetics, PNAS, and Blood, which have been cited over 12,000 times. He has also received many awards, including the Ho Leung Ho Lee Award for Science and Technology, the Qui-Shi Award for Outstanding Young Scientist from China, the Cheung Kong Scholars Achievement Award, Prix de l ´Oise from La Ligue Nationale contre le Cancer of France, and the National Foundation for Cancer Research’s Szent-Györgyi Prize for Progress in Cancer Research. He is a member of the Chinese Academy of Sciences, a foreign associate of the National Academy of Sciences and the Institute of Medicine of the United States and the French Academy of Sciences, a foreign member of The Royal Society of the United Kingdom, and a member of the Academy of Sciences for the Developing World. Dr. Chen is also an honorary fellow of the UK Academy of Medical Science and external scientific member of the Max Planck Institute of Molecular Genetics in Germany. 

「Thirty years ago, APL was among the most dreaded and lethal forms of leukemia. Today, it is among the most curable, thanks to the outstanding contributions of Drs. de Thé and Chen,」 said ASH President Charles S. Abrams, MD, of the University of Pennsylvania. 「Together, their work to understand APL from a molecular level, and then applying those insights to discovering groundbreaking treatments, has significantly improved patient outcomes. Drs. de Thé and Chen’s accomplishments are highly regarded in our field, and I am honored that the Society has chosen them to give one of our most prestigious lectures."

编辑: 张莹

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