Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment
Abstract
1. Introduction
General Considerations for Myelodysplastic Syndromes
2. Risk Stratification and Treatment Options
Prognostic Tools and Standard Treatment Approaches
3. New Treatment Approaches
Overview of Innovative Therapies Under Clinical Development
4. Oxidative Stress: Mechanisms and Disease Connections
4.1. Oxidative Stress Plays a Role in Both Physiological and Pathological Contexts
4.2. Oxidative Stress and Mitochondrial Dysfunction in Cancer Biology and Therapy Response
5. Oxidative Stress in Myelodysplastic Syndromes
5.1. Oxidative Mechanisms Specific to MDS Pathogenesis
5.2. The Dual Role of Reactive Oxygen Species in the Pathogenesis of Myelodysplastic Syndromes
5.3. Impacts of Iron Dysregulation and Chelation Therapy on Oxidative Stress in Myelodysplastic Syndrome
5.4. Mitochondrial Dynamics and Ferroptosis in the Metabolic Landscape of Myelodysplastic Syndromes
5.5. DNA Methylation and Epigenetic Regulation in Myelodysplastic Syndromes: Biomarkers and Functional Implications
5.6. Oxidative Stress in MDS and the Treatment Options Available
6. Future Perspectives in Oxidative Stress Research: The Role of Artificial Intelligence in Antioxidant Discovery in Myeloid Malignancies
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Mechanism | Molecular Drivers | Cellular Impact | Therapeutic Strategies |
---|---|---|---|
DNA Damage | ROS, RNS | Genomic instability, mutations, apoptosis | Antioxidants, DNA repair enhancers |
Mitochondrial Dysfunction | Iron overload, mtDNA mutations | Altered energy metabolism, increased ROS | Iron chelators (deferasirox), mitochondrial-targeted therapies |
Epigenetic Alterations | TET2, DNMT3A, CEBPA methylation | Aberrant gene expression, impaired differentiation | HMAs, vitamin C (TET cofactor) |
Redox Imbalance | Low GSH, high NOX activity | Sustained oxidative stress, ineffective hematopoiesis | GSH donors, NOX inhibitors |
Immune Dysfunction | NK cells, inflammatory cytokines | Impaired immune surveillance | Immunomodulators, azacitidine |
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Pierro, F.; Fazio, M.; Murdaca, G.; Stagno, F.; Gangemi, S.; Allegra, A. Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment. Int. J. Mol. Sci. 2025, 26, 6415. https://doi.org/10.3390/ijms26136415
Pierro F, Fazio M, Murdaca G, Stagno F, Gangemi S, Allegra A. Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment. International Journal of Molecular Sciences. 2025; 26(13):6415. https://doi.org/10.3390/ijms26136415
Chicago/Turabian StylePierro, Federico, Manlio Fazio, Giuseppe Murdaca, Fabio Stagno, Sebastiano Gangemi, and Alessandro Allegra. 2025. "Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment" International Journal of Molecular Sciences 26, no. 13: 6415. https://doi.org/10.3390/ijms26136415
APA StylePierro, F., Fazio, M., Murdaca, G., Stagno, F., Gangemi, S., & Allegra, A. (2025). Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment. International Journal of Molecular Sciences, 26(13), 6415. https://doi.org/10.3390/ijms26136415