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血液学中的表观遗传学革命:从实验室突破到临床变革。

The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.

作者信息

Abdar Esfahani Mahdis, Servatian Nazli, Al-Athari Ali Jihad Hemid, Khafaja Elaf Salah Mehdi, Rahmani Seraji Hamideh, Soleimani Samarkhazan Hamed

机构信息

Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Bushehr University of Medical Sciences, Bushehr, Iran.

Cord Blood Bank Laboratory Department, Royan Stem Cell Technology Company, Tehran, Iran.

出版信息

Clin Exp Med. 2025 Jul 1;25(1):230. doi: 10.1007/s10238-025-01783-z.

Abstract

The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransferase inhibitors (e.g., azacitidine and decitabine), histone deacetylase inhibitors (e.g., vorinostat and romidepsin), and enhancer of zeste homologue 2 inhibitors (e.g., tazmetostat), demonstrates the potential to reverse aberrant epigenetic modifications and restoring normal cellular functions. Moreover, we highlight innovative therapeutic approaches, including combination therapies and CRISPR-based epigenetic editing tools, which are influencing the future of treatment for hematological malignancies. Despite promising results, challenges such as off-target effects, drug resistance, and the need for personalized approaches remain significant barriers to effective treatment. We emphasize that further study is required to improve delivery systems, comprehend resistance mechanisms and develop precision medicine strategies that can tailor therapies to individual patient profiles. By integrating benchside discoveries with clinical applications, this review aims to illuminate the transformative potential of epigenetic therapies in improving patient outcomes in hematology.

摘要

随着表观遗传过程被公认为血液系统恶性肿瘤发生发展的重要因素,血液学领域经历了重大变革。本文综述探讨了表观遗传改变,即DNA甲基化和组蛋白修饰,对急性髓系白血病和骨髓增生异常综合征等疾病的发生和进展的影响。我们讨论了这些表观遗传修饰如何导致基因表达失调,最终促进白血病发生。表观遗传疗法的出现,如DNA甲基转移酶抑制剂(如阿扎胞苷和地西他滨)、组蛋白去乙酰化酶抑制剂(如伏立诺他和罗米地辛)以及zeste同源物2抑制剂(如他泽司他),显示了逆转异常表观遗传修饰和恢复正常细胞功能的潜力。此外,我们强调了创新的治疗方法,包括联合疗法和基于CRISPR的表观遗传编辑工具,这些正在影响血液系统恶性肿瘤治疗的未来。尽管取得了令人鼓舞的结果,但脱靶效应、耐药性以及个性化治疗需求等挑战仍然是有效治疗的重大障碍。我们强调需要进一步研究以改进给药系统、理解耐药机制并制定能够根据个体患者情况量身定制治疗方案的精准医学策略。通过将实验室研究发现与临床应用相结合,本综述旨在阐明表观遗传疗法在改善血液学患者预后方面的变革潜力。

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