The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia-A Promising Road Ahead.

IF 4.5 2区 医学 Q1 ONCOLOGY
Cancers Pub Date : 2025-03-17 DOI:10.3390/cancers17061009
Piotr Strzałka, Kinga Krawiec, Aneta Wiśnik, Dariusz Jarych, Magdalena Czemerska, Izabela Zawlik, Agnieszka Pluta, Agnieszka Wierzbowska
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引用次数: 0

Abstract

Acute myeloid leukemia (AML) corresponds to a heterogeneous group of clonal hematopoietic diseases, which are characterized by uncontrolled proliferation of malignant transformed myeloid precursors and their inability to differentiate into mature blood cells. The prognosis of AML depends on many variables, including the genetic features of the disease. Treatment outcomes, despite the introduction of new targeted therapies, are still unsatisfactory. Recently, there have been an increasing number of reports on enzymatic proteins of the sirtuin family and their potential importance in cancer in general. Sirtuins are a group of 7 (SIRT1-7) NAD+-dependent histone deacetylases with pleiotropic effects on metabolism, aging processes, and cell survival. They are not only responsible for post-translational modification of histones but also play various biochemical functions and interact with other proteins regulating cell survival, such as p53. Thus, their role in key mechanisms of tumorigenesis makes them a worthwhile topic in AML. Different sirtuins have been shown to act oppositely depending on the biological context, the mechanism of which requires further exploration. This review provides a comprehensive description of the significance and role of sirtuins in AML in light of the current state of knowledge. It focuses in particular on molecular mechanisms regulated by sirtuins and signaling pathways involved in leukemogenesis, as well as clinical aspects and potential therapeutic targets in AML.

急性髓性白血病(AML)是一组异质性克隆性造血疾病,其特点是恶性转化的髓系前体不受控制地增殖,并且无法分化为成熟的血细胞。急性髓细胞性白血病的预后取决于许多变量,包括疾病的遗传特征。尽管引入了新的靶向疗法,但治疗效果仍不令人满意。最近,有关 sirtuin 家族酶蛋白及其在癌症中的潜在重要性的报道越来越多。Sirtuins 是由 7 种(SIRT1-7)依赖 NAD+ 的组蛋白去乙酰化酶组成的,对新陈代谢、衰老过程和细胞存活具有多方面的影响。它们不仅负责组蛋白的翻译后修饰,还发挥着各种生化功能,并与其他调节细胞存活的蛋白(如 p53)相互作用。因此,它们在肿瘤发生关键机制中的作用使其成为急性髓细胞性白血病中一个值得研究的课题。研究表明,不同的sirtuins在不同的生物环境中会产生相反的作用,其机制有待进一步探讨。本综述根据目前的知识水平,全面阐述了sirtuins在急性髓细胞性白血病中的意义和作用。它特别关注sirtuins调控的分子机制、参与白血病发生的信号通路,以及急性髓细胞性白血病的临床方面和潜在治疗靶点。
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
Cancers
Cancers Medicine-Oncology
CiteScore
8.00
自引率
9.60%
发文量
5371
审稿时长
18.07 days
期刊介绍: Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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