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急性淋巴细胞白血病的表观遗传学修饰:从细胞机制到治疗。

Epigenetic Modifications in Acute Lymphoblastic Leukemia: From Cellular Mechanisms to Therapeutics.

机构信息

Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Curr Gene Ther. 2021;21(1):60-71. doi: 10.2174/1566523220999201111194554.

Abstract

BACKGROUND

Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood, and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic alterations as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, beyond available conventional therapy.

OBJECTIVE

This review will focus on a better understanding of the epigenetic mechanisms in cancer development and progression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and microRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel, well-suited approaches against ALL.

CONCLUSION

According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifications, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

摘要

背景

表观遗传修饰模式被认为是血液恶性肿瘤的特征。DNA 甲基化调节剂的修饰在淋巴瘤和白血病中经常发生,因此不同的甲基化模式定义了不同类型的白血病。一般来说,对表观遗传学的作用了解较少,大多数研究集中在遗传异常和细胞遗传学研究上,以开发血液系统疾病患者的新治疗方法。最近,了解急性淋巴细胞白血病(ALL)的潜在机制,特别是表观遗传改变作为 ALL 发展的驱动力,为开发有前途的策略开辟了一个新的研究时代,超越了现有的常规治疗。

目的

本综述将重点关注癌症发展和进展中的表观遗传机制,特别强调 ALL 中的表观遗传改变,包括 DNA 甲基化、组蛋白修饰和 microRNA 改变。其他将讨论的主题包括将表观遗传改变用作有希望的治疗靶点,以开发针对 ALL 的新型、合适的方法。

结论

根据文献综述,ALL 的白血病发生受到表观遗传修饰的广泛影响,特别是 DNA 超甲基化、组蛋白修饰和 miRNA 改变。

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