Yusoff Nur Afizah, Abd Hamid Zariyantey, Taib Izatus Shima, Abdul Razak Siti Razila, Budin Siti Balkis
Centre for Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Department of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Pulau Pinang, Malaysia.
Adv Exp Med Biol. 2025;1483:49-67. doi: 10.1007/5584_2024_846.
Epigenetic regulation in hematopoietic stem cells (HSCs) research has emerged as a transformative molecular approach that enhances understanding of hematopoiesis and hematological disorders. This chapter investigates the intricate epigenetic mechanisms that control HSCs function, including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. It also explores the role of non-coding ribonucleic acid (RNAs) as epigenetic regulators, highlighting how changes in gene expression can occur without alterations to the DNA sequence. Epigenetic mechanisms play a pivotal in regulating HSC self-renewal and differentiation, processes essential for maintaining a balanced hematopoietic system in which lineage-specific hematopoietic stem and progenitor cells (HSPCs) pool is sustained. Recent advancements in epigenetic mapping and sequencing technologies have illuminated the dynamic epigenetic landscapes that characterize HSCs and their progeny. Numerous studies have revealed that dysregulation of epigenetic pathways is a hallmark of various hematological malignancies, including leukemias, lymphomas, and myelodysplastic syndromes. This review highlights key findings that demonstrate the impact of epigenetic abnormalities on the disruption of HSPC niches and the progression of oncogenesis in hematological malignancies. Furthermore, this chapter explores the therapeutic potential of targeting epigenetic modifications that are critical in formation and progression of hematologic malignancies. It also discusses the latest developments in epigenetic therapies, including the use of DNA methyltransferase inhibitors, histone deacetylase inhibitors, and emerging drugs targeting other epigenetic regulators. These therapies represent a promising strategy for resetting aberrant epigenetic states, potentially restoring normal hematopoiesis. Conclusively, this chapter offers a thorough overview of the current landscape and future directions of epigenetic research related to the maintenance of the HSPC niches. The insights presented here aim to contribute significantly to the field, offering a reference point for molecular approaches that enhance our understanding of hematopoiesis and its associated hematological malignancies.
造血干细胞（HSCs）研究中的表观遗传调控已成为一种变革性的分子方法，可增进对造血作用和血液系统疾病的理解。本章研究了控制造血干细胞功能的复杂表观遗传机制，包括脱氧核糖核酸（DNA）甲基化、组蛋白修饰和染色质重塑。它还探讨了非编码核糖核酸（RNAs）作为表观遗传调节因子的作用，强调了基因表达如何在不改变DNA序列的情况下发生变化。表观遗传机制在调节造血干细胞的自我更新和分化中起着关键作用，而这些过程对于维持一个平衡的造血系统至关重要，在该系统中，谱系特异性造血干细胞和祖细胞（HSPCs）库得以维持。表观遗传图谱和测序技术的最新进展揭示了表征造血干细胞及其后代的动态表观遗传景观。大量研究表明，表观遗传途径的失调是各种血液系统恶性肿瘤的标志，包括白血病、淋巴瘤和骨髓增生异常综合征。本综述强调了关键发现，这些发现证明了表观遗传异常对造血干细胞微环境破坏和血液系统恶性肿瘤肿瘤发生进展的影响。此外，本章探讨了针对在血液系统恶性肿瘤形成和进展中起关键作用的表观遗传修饰的治疗潜力。它还讨论了表观遗传治疗的最新进展，包括DNA甲基转移酶抑制剂、组蛋白脱乙酰酶抑制剂以及针对其他表观遗传调节因子的新兴药物的使用。这些疗法代表了一种有前景的策略，用于重置异常的表观遗传状态，有可能恢复正常造血。总之，本章全面概述了与造血干细胞微环境维持相关的表观遗传研究的当前状况和未来方向。此处提出的见解旨在为该领域做出重大贡献，为增强我们对造血作用及其相关血液系统恶性肿瘤理解的分子方法提供参考点。
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