白血病的精准基因组医学研究与转化应用

doi:10.16288/j.yczz.18-188

遗传 ›› 2018, Vol. 40 ›› Issue (11): 988-997.doi: 10.16288/j.yczz.18-188

白血病的精准基因组医学研究与转化应用

于雪新,陈艾莉,李玥莹,刘丹,王前飞()

中国科学院北京基因组研究所,中国科学院精准基因组医学重点实验室,北京 100101

收稿日期:2018-07-03 修回日期:2018-09-12 出版日期:2018-11-20 发布日期:2018-09-13
作者简介:于雪新,博士,助理研究员,研究方向：白血病生物信息学。E-mail: yuxx@big.ac.cn

Precision genomic and translational medicine for acute myeloid leukemia

Xuexin Yu,Aili Chen,Yueying Li,Dan Liu,Qianfei Wang()

CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Bejijng 100101, China

Received:2018-07-03 Revised:2018-09-12 Published:2018-11-20 Online:2018-09-13

摘要/Abstract

摘要：

白血病是常见的血液系统恶性肿瘤,治疗主要以化疗为主,但总体治疗效果欠佳且发病的分子机制不明。因此,白血病的发病机制以及临床研究急需新的突破口。近年来,研究人员不仅发现了急性髓系白血病耐药的新靶点,揭示不同表观修饰的相互作用加速MLL白血病进展,也阐释了NK细胞白血病发病机制,发现关键表观因子在髓系肿瘤发生中的重要功能。尤其是新抑癌基因SETD2的发现,为急性髓系白血病的治疗提供了新的靶点。此外,在国际上研究人员首次将低剂量化疗方案用于治疗初诊儿童急性髓系白血病,在不影响疗效的基础上显著降低了化疗毒副作用及治疗费用。虽然基因组特征的解析加深了我们对癌症生物学分子机制的理解,但是近年来的研究表明瘤内异质性的克隆演化也是导致白血病临床治疗效果不佳的主要因素,解析不同化疗方案下白血病患者不同的克隆演化模式及其在临床预后评估中的作用是目前的研究热点之一。上述研究为急性髓系白血病诊断及治疗方法的改进提供了新的契机。

关键词: 白血病, 机制, SETD2, 低剂量化疗, 克隆演化, 精准医学

Abstract:

Leukemia is a group of hematologic malignancy that has unfavorable prognosis and unclear mechanisms. In recent years, advances in leukemia research encompass the discovery of novel targets in acute myeloid leukemia drug resistance, epigenetic crosstalk in mixed lineage leukemia (MLL) leukemogenesis, genetic mechanisms of aggressive NK-cell leukemia, as well as the critical role of key epigenetic regulator in acute myeloid malignancy. Remarkably, researchers revealed that the histone modifying gene SETD2 as a new tumor suppressor and therapeutic target in patients with acute myeloid leukemia. Furthermore, low-dose chemotherapy as a frontline regiment in treating pediatric acute myeloid leukemia can substantially reduce the toxic side effects and treatment costs without impairing efficacy. Although advances in cancer genomics have greatly increased our understanding of the molecular characteristics in tumor biology, recent studies suggest that Darwinian evolution of intratumor heterogeneity represents a major challenge to develop therapeutic strategies to improve disease control. Researchers also dissected the distinct evolutionary dynamics under different chemotherapy regimens and the corresponding applications in the evaluation of treatment outcomes. Altogether, these efforts offered new opportunities for the development of acute myeloid leukemia diagnostics and therapeutics.

Key words: leukemia, mechanism, SETD2, low-dose therapy, clonal evolution, precision medicine

于雪新,陈艾莉,李玥莹,刘丹,王前飞. 白血病的精准基因组医学研究与转化应用[J]. 遗传, 2018, 40(11): 988-997.

Xuexin Yu,Aili Chen,Yueying Li,Dan Liu,Qianfei Wang. Precision genomic and translational medicine for acute myeloid leukemia[J]. Hereditas(Beijing), 2018, 40(11): 988-997.

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白血病的精准基因组医学研究与转化应用

Precision genomic and translational medicine for acute myeloid leukemia

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