Pierro Federico, Fazio Manlio, Murdaca Giuseppe, Stagno Fabio, Gangemi Sebastiano, Allegra Alessandro
Division of Hematology, Department of Human Pathology in Adulthood and Childhood "Gaetano Barresi", University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Department of Internal Medicine, University of Genova, 16126 Genova, Italy.
Int J Mol Sci. 2025 Jul 3;26(13):6415. doi: 10.3390/ijms26136415.
Myelodysplastic syndromes are a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral cytopenia, and dysplasia in one or more myeloid lineages, with a variable risk of progression to acute myeloid leukemia. In addition to well-characterized genetic and epigenetic abnormalities, oxidative stress has emerged as a critical contributor to the pathophysiology of myelodysplastic syndrome. Reactive oxygen species and reactive nitrogen species can induce cumulative DNA damage, mitochondrial dysfunction, and altered redox homeostasis, promoting genomic instability and clonal evolution. Elevated oxidative stress in patients with myelodysplastic syndromes has been linked to increased apoptosis of hematopoietic stem and progenitor cells, disruption of the bone marrow microenvironment, and progression toward leukemic transformation. Moreover, ROS-related pathways, such as TP53 mutations and epigenetic dysregulation, interact with the key molecular drivers of myelodysplastic syndrome. Given these findings, oxidative stress is now recognized not only as a hallmark of disease biology but also as a potential therapeutic target. Antioxidant-based strategies and agents that modulate redox signaling are being investigated for their ability to restore hematopoietic function and enhance treatment efficacy. This review provides an overview of the current biology of myelodysplastic syndrome, highlights the connections between oxidative stress and disease mechanisms, and explores emerging redox-targeted therapeutic approaches.
骨髓增生异常综合征是一组克隆性造血干细胞疾病，其特征为造血无效、外周血细胞减少以及一个或多个髓系谱系发育异常，并具有进展为急性髓系白血病的可变风险。除了已明确的遗传和表观遗传异常外，氧化应激已成为骨髓增生异常综合征病理生理学的关键因素。活性氧和活性氮可诱导累积的DNA损伤、线粒体功能障碍以及氧化还原稳态改变，促进基因组不稳定和克隆进化。骨髓增生异常综合征患者氧化应激升高与造血干细胞和祖细胞凋亡增加、骨髓微环境破坏以及向白血病转化的进展有关。此外，ROS相关途径，如TP53突变和表观遗传失调，与骨髓增生异常综合征的关键分子驱动因素相互作用。鉴于这些发现，氧化应激现在不仅被认为是疾病生物学的一个标志，也是一个潜在的治疗靶点。基于抗氧化剂的策略和调节氧化还原信号的药物正在研究其恢复造血功能和提高治疗效果的能力。本综述概述了骨髓增生异常综合征的当前生物学，强调了氧化应激与疾病机制之间的联系，并探讨了新兴的氧化还原靶向治疗方法。
