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.
急性髓系白血病（AML）是一组异质性的克隆性造血系统疾病，其特征是恶性转化的髓系前体细胞不受控制地增殖，且无法分化为成熟血细胞。AML的预后取决于多种变量，包括疾病的遗传学特征。尽管引入了新的靶向治疗，其治疗效果仍不尽如人意。近年来，关于sirtuin家族酶蛋白及其在癌症中潜在重要性的报道日益增多。Sirtuins是一类由7个成员（SIRT1-7）组成的NAD+依赖性组蛋白去乙酰化酶，对代谢、衰老过程和细胞存活具有多效性作用。它们不仅负责组蛋白的翻译后修饰，还发挥多种生化功能，并与p53等其他调控细胞存活的蛋白质相互作用。因此，它们在肿瘤发生关键机制中的作用使其成为AML研究中值得关注的课题。研究表明，不同的sirtuin蛋白在特定生物学背景下可能发挥相反的作用，其具体机制有待进一步探索。本综述基于现有知识，全面阐述了sirtuins在AML中的意义与作用，重点聚焦于sirtuins调控的分子机制、参与白血病发生的信号通路，以及AML的临床特征和潜在治疗靶点。
The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia—A Promising Road Ahead
肿瘤(癌症)患者之家