Epigenetic alterations in AML: Deregulated functions leading to new therapeutic options.

3区生物学 Q1 Biochemistry, Genetics and Molecular Biology

International review of cell and molecular biology Pub Date : 2024-01-01 Epub Date: 2024-07-09 DOI:10.1016/bs.ircmb.2024.06.003

Kourosh Hayatigolkhatmi, Riccardo Valzelli, Oualid El Menna, Saverio Minucci

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引用次数: 0

Abstract

Acute myeloid leukemia (AML) results in disruption of the hematopoietic differentiation process. Crucial progress has been made, and new therapeutic strategies for AML have been developed. Induction chemotherapy, however, remains the main option for the majority of AML patients. Epigenetic dysregulation plays a central role in AML pathogenesis, supporting leukemogenesis and maintenance of leukemic stem cells. Here, we provide an overview of the intricate interplay of altered epigenetic mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, in AML development. We explore the role of epigenetic regulators, such as DNMTs, HMTs, KDMs, and HDACs, in mediating gene expression patterns pushing towards leukemic cell transformation. Additionally, we discuss the impact of cytogenetic lesions on epigenomic remodeling and the potential of targeting epigenetic vulnerabilities as a therapeutic strategy. Understanding the epigenetic landscape of AML offers insights into novel therapeutic avenues, including epigenetic modifiers and particularly their use in combination therapies, to improve treatment outcomes and overcome drug resistance.

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急性髓细胞性白血病的表观遗传学改变：功能失调带来新的治疗方案。

急性髓性白血病（AML）导致造血分化过程中断。目前，急性髓细胞白血病的治疗已取得重大进展，并已开发出新的治疗策略。然而，诱导化疗仍是大多数急性髓细胞白血病患者的主要选择。表观遗传失调在急性髓细胞性白血病发病机制中起着核心作用，支持着白血病的发生和白血病干细胞的维持。在此，我们概述了表观遗传机制改变在急性髓细胞性白血病发病过程中错综复杂的相互作用，包括DNA甲基化、组蛋白修饰和染色质重塑。我们探讨了表观遗传调控因子（如 DNMT、HMT、KDM 和 HDAC）在介导基因表达模式推动白血病细胞转化中的作用。此外，我们还讨论了细胞遗传病变对表观基因组重塑的影响，以及以表观基因漏洞为靶点作为治疗策略的潜力。通过了解急性髓细胞性白血病的表观遗传学特征，我们可以发现新的治疗途径，包括表观遗传修饰剂，尤其是在联合疗法中使用表观遗传修饰剂，以改善治疗效果并克服耐药性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International review of cell and molecular biology BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY

CiteScore

7.70

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： International Review of Cell and Molecular Biology presents current advances and comprehensive reviews in cell biology-both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.