AML的表观遗传改变：放松管制功能，导致新的治疗选择
Epigenetic alterations in AML: Deregulated functions leading to new therapeutic options
影响因子:6.42000
发表日期:2024
作者:
Kourosh Hayatigolkhatmi, Riccardo Valzelli, Oualid El Menna, Saverio Minucci
摘要
急性髓样白血病（AML）导致造血分化过程中断。已经取得了关键的进步，并制定了新的AML治疗策略。然而，诱导化疗仍然是大多数AML患者的主要选择。表观遗传失调在AML发病机理中起着核心作用，支持白血病干细胞的白血病和维持。在这里，我们概述了改变的表观遗传机制的复杂相互作用，包括DNA甲基化，组蛋白修饰和染色质重塑，在AML发育中。我们探讨了表观遗传调节剂，例如DNMT，HMTS，KDM和HDACS，在介导基因表达模式的介导，推向白血病细胞转化。此外，我们讨论了细胞遗传病变对表观基因组重塑的影响，以及将表观遗传脆弱性作为治疗策略的潜力。了解AML的表观遗传景观提供了对新型治疗途径的见解，包括表观遗传学修饰剂，尤其是它们在组合疗法中的使用，以改善治疗结果并克服耐药性。
Abstract
Acute myeloid leukemia (AML) results in disruption of the hematopoietic differentiation process. Crucial progress has been made, and new therapeutic strategies for AML have been developed. Induction chemotherapy, however, remains the main option for the majority of AML patients. Epigenetic dysregulation plays a central role in AML pathogenesis, supporting leukemogenesis and maintenance of leukemic stem cells. Here, we provide an overview of the intricate interplay of altered epigenetic mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, in AML development. We explore the role of epigenetic regulators, such as DNMTs, HMTs, KDMs, and HDACs, in mediating gene expression patterns pushing towards leukemic cell transformation. Additionally, we discuss the impact of cytogenetic lesions on epigenomic remodeling and the potential of targeting epigenetic vulnerabilities as a therapeutic strategy. Understanding the epigenetic landscape of AML offers insights into novel therapeutic avenues, including epigenetic modifiers and particularly their use in combination therapies, to improve treatment outcomes and overcome drug resistance.