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组蛋白去乙酰化酶抑制剂:靶向表观遗传调控治疗急性白血病

Histone deacetylase inhibitors: targeting epigenetic regulation in the treatment of acute leukemia.

作者信息

Xiao Tong, Chen Zhigang, Xie Yutong, Yang Chao, Wu Junhong, Gao Lei

机构信息

Medical Center of Hematology, State Key Laboratory of Trauma, Burn and Combined Injury, Xinqiao Hospital, Army Medical University, Chongqing, China.

Medical Center of Hematology, State Key Laboratory of Trauma, Burn and Combined Injury, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing 400037, China.

出版信息

Ther Adv Hematol. 2024 Oct 16;15:20406207241283277. doi: 10.1177/20406207241283277. eCollection 2024.

Abstract

Acute leukemia (AL) is a rare yet perilous malignancy. Currently, the primary treatment for AL involves combination chemotherapy as the cornerstone of comprehensive measures, alongside hematopoietic stem cell transplantation as a radical approach. However, despite these interventions, mortality rates remain high, particularly among refractory/recurrent patients or elderly individuals with a poor prognosis. Acetylation, a form of epigenetic regulation, has emerged as a promising therapeutic avenue for treating AL. Recent studies have highlighted the potential of acetylation regulation as a novel treatment pathway. Histone deacetylase inhibitors (HDACis) play a pivotal role in modulating the differentiation and development of tumor cells through diverse pathways, simultaneously impacting the maturation and function of lymphocytes. HDACis demonstrate promise in enhancing survival rates and achieving a complete response in both acute myeloid leukemia and acute T-lymphoblastic leukemia patients. This article provides a comprehensive review of the advancements in HDACi therapy for AL, shedding light on its potential implications for clinical practice.

摘要

急性白血病(AL)是一种罕见但危险的恶性肿瘤。目前,AL的主要治疗方法是以联合化疗为综合措施的基石,同时将造血干细胞移植作为一种根治性方法。然而,尽管采取了这些干预措施,死亡率仍然很高,尤其是在难治性/复发性患者或预后较差的老年患者中。乙酰化作为一种表观遗传调控形式,已成为治疗AL的一种有前景的治疗途径。最近的研究强调了乙酰化调控作为一种新的治疗途径的潜力。组蛋白去乙酰化酶抑制剂(HDACis)通过多种途径在调节肿瘤细胞的分化和发育中起关键作用,同时影响淋巴细胞的成熟和功能。HDACis在提高急性髓系白血病和急性T淋巴细胞白血病患者的生存率及实现完全缓解方面显示出前景。本文全面综述了HDACi治疗AL的进展,阐明了其对临床实践的潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3f9/11483798/53a87d578ee0/10.1177_20406207241283277-fig1.jpg

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