REVIEW article
Front. Oncol.
Sec. Hematologic Malignancies
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1655486
This article is part of the Research TopicMyelodysplastic Neoplasm and Acute Myeloid Leukemia: Multi-Omics Approaches and Precision MedicineView all 8 articles
TP53-Mutated MDS and AML: Immune Dysregulation, Tumor Microenvironment, and Emerging Therapeutic Strategies
Provisionally accepted
- Taibah University, Medina, Saudi Arabia
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TP53 mutations drive oncogenesis and therapeutic resistance in myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML), impairing p53-regulated functions such as apoptosis, immune surveillance, and genomic stability, leading to immune evasion and metabolic reprogramming. The tumor microenvironment in TP53-mutated MDS and AML fosters leukemic progression through cytokine dysregulation, altered metabolism, and immune suppression. Current therapies, including chemotherapy and hypomethylating agents, offer limited efficacy, resulting in poor overall survival rates for these high-risk patients. However, novel therapeutic approaches provide promising avenues, including MDM2 inhibitors, p53-reactivating agents, pathway-targeted inhibitors (Hedgehog, Wnt, NF-κB), immune modulation (checkpoint inhibitors, CAR-T therapy), metabolic interventions (fatty acid metabolism, glycolysis), and gene-editing technologies (CRISPR/Cas9, base editing). This review explores the mechanisms of immune dysfunction in TP53-mutated MDS and AML while highlighting emerging therapeutic strategies, emphasizing the integration of targeted, metabolic, and immune-modulating therapies as a transformative approach to improve patient outcomes.
Keywords: TP53 mutation, Myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), Immune Evasion, Tumor Microenvironment, targeted therapies
Received: 28 Jun 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Albakri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Marwah M Albakri, Taibah University, Medina, Saudi Arabia
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