急性髓细胞白血病中DNA甲基化与缺氧之间的串扰。

IF 5.7 2区 医学 Q1 Medicine
Sam Humphries, Danielle R Bond, Zacary P Germon, Simon Keely, Anoop K Enjeti, Matthew D Dun, Heather J Lee
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引用次数: 0

摘要

背景:急性髓细胞白血病(AML)是一种致命的疾病,其特征是骨髓中未成熟髓细胞的增殖失控。DNA甲基化调节的改变是AML的重要表观遗传学驱动因素,缺氧的骨髓微环境有助于促进白血病的发生。因此,表观遗传学调控和缺氧信号之间的相互作用将对AML的发展和治疗具有重要意义。正文:这篇综述总结了DNA甲基化和缺氧骨髓微环境在AML的发展、进展和治疗中的重要性。在这里,我们关注缺氧在信号传导和随后的DNA甲基化调控中所起的作用。缺氧可能通过改变代谢途径、表观遗传调控因子的转录控制以及对表观遗传修饰因子的酶活性的直接影响来影响DNA甲基化。DNA甲基化也可能阻止缺氧反应基因的激活,表明表观遗传调控和缺氧微环境之间存在双向串扰。最后,我们考虑了这些相互作用的临床意义,表明缺氧骨髓中细胞循环的减少可能会降低低甲基化药物的疗效。结论:缺氧可能通过与DNA甲基化的复杂相互作用影响AML的进展,其中低甲基化药物的治疗效果可能在缺氧的骨髓中受到限制。因此,为了实现AML患者的最佳结果,未来的研究应考虑联合治疗,以促进骨髓中AML细胞的循环或促进其从骨髓中分离。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.

Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.

Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.

Background: Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment.

Main body: This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents.

Conclusion: Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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