文章摘要

表观遗传学调控及治疗在急性髓系白血病中的研究进展

作者: 1郭丹, 1李英花
1 哈尔滨医科大学附属第一医院血液内科,哈尔滨 150001
通讯: 李英花 Email: yinghualihmu@126.com
DOI: 10.3978/j.issn.2095-6959.2021.06.028
基金: 黑龙江省科研计划项目(201708)。

摘要

急性髓系白血病(acute myeloid leukemia,AML)是一类高度异质性、来源于造血干/祖细胞的恶性克隆性疾病,尽管免疫治疗、靶向治疗、联合化疗等治疗策略在不断优化和完善,但在耐药复发、疾病进展等严峻挑战下,AML患者的长期生存仍未得到明显改善。表观遗传学修饰与AML的发生、进展密切相关,其中DNA甲基化、组蛋白修饰、染色质结构重塑和非编码RNA调控机制在基因的转录、表达及细胞的增殖、凋亡等过程中发挥至关重要的作用。随着DNA甲基转移酶抑制剂、组蛋白去乙酰化酶抑制剂等表观遗传药物的深入研究和临床应用,AML个体精准化治疗水平明显提高,且表观遗传药物联合以及与其他抗肿瘤药物联合的治疗方案具有良好的临床应用前景,值得人们进一步探索和研究,并为不可耐受高强度化疗和复发/难治性AML患者的治疗提供新的思路和方向。
关键词: 急性髓系白血病;表观遗传学修饰;表观遗传学治疗;联合治疗

Research progress of epigenetic regulation and therapy in acute myeloid leukemia

Authors: 1GUO Dan, 1LI Yinghua
1 Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China

CorrespondingAuthor: LI Yinghua Email: yinghualihmu@126.com

DOI: 10.3978/j.issn.2095-6959.2021.06.028

Foundation: This work was supported by the Scientific Research Project of Heilongjiang Province, China (201708).

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous malignant clonal disease derived from hematopoietic stem cells. Although treatment strategies, such as immunotherapy, targeted therapy, and combination chemotherapy are constantly optimized and improved, the long-term survival of AML patients has not been significantly prolonged under the severe challenges of drug resistance, relapse, and disease progression. Epigenetic modifications are closely associated with the pathogenesis and progression of AML, and the regulatory mechanisms of DNA methylation, histone modification, chromatin structure remodeling, and the non-coding RNA play essential roles in the processes of gene transcription, gene expression, cell proliferation and apoptosis. With the intensive researches and clinical applications of epigenetic drugs, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, the level of individual precise treatment in AML has been significantly improved. Moreover, the combination therapies between epigenetic drugs and other anti-tumor drugs have shown great clinical application prospects, and further explorations should be strongly encouraged, as well as to provide new ideas and directions for treatments of AML patients intolerant of intensive chemotherapy and relapsed/refractory AML patients.
Keywords: acute myeloid leukemia; epigenetic modification; epigenetic therapy; combination therapy