Waldenström Macroglobulinemia: The Role of TP53 Mutations in Disease Progression and Therapeutic Response

• Published in: Current Issues in Molecular Biology
• Main Authors: Despoina Dimitria Kampitsi, Paschalis Theotokis, Paschalis Evangelidis, Soultana Meditskou, Maria Eleni Manthou, Iasonas Dermitzakis
• Format: Article
• Language: English
• Published: MDPI AG 2025-04-01
• Subjects: prognosis; TP53; treatment; Waldenström Macroglobulinemia
• Online Access: https://www.mdpi.com/1467-3045/47/4/260
• ISSN: 1467-3037; 1467-3045

Waldenström Macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder characterized by the production of monoclonal IgM paraprotein and infiltration of the bone marrow by lymphoplasmacytic cells. While WM generally exhibits a slow clinical course, it has the potential to progress into more aggressive hematologic malignancies, such as diffuse large B-cell lymphoma. The <i>TP53</i> gene, often referred to as the “guardian of the genome”, plays a pivotal role in maintaining genomic stability, regulating the cell cycle, and orchestrating apoptosis. Mutations in <i>TP53</i> undermine these essential processes, resulting in dysregulated cellular proliferation, defective apoptotic mechanisms, and genomic instability—hallmarks of cancer development. Although <i>TP53</i> mutations have been extensively investigated in several hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndromes, and chronic lymphocytic leukemia, their role in WM remains underexplored. Emerging evidence suggests that <i>TP53</i> mutations may have a significant impact on the disease progression and therapeutic response in WM. This review examines the current knowledge of <i>TP53</i> mutations in WM, highlighting their implications for prognosis and therapeutic strategies. A deeper understanding of the role of <i>TP53</i> in WM could provide critical insights for improving disease management and advancing the development of targeted therapies.