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REVIEW article

Front. Oncol.

Sec. Hematologic Malignancies

This article is part of the Research TopicUpdates on the Management of Hematologic Malignancies from SOHO Italy: Educational Insights and Clinical PerspectivesView all 10 articles

TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Comprehensive Overview of Targeted Approaches

Provisionally accepted
Shweta Ravindra DeshpandeShweta Ravindra Deshpande1Wing Fai LiWing Fai Li2Junmin SongJunmin Song2Mark ForsbergMark Forsberg3Claudio CerchioneClaudio Cerchione4Giovanni MartinelliGiovanni Martinelli5Marina KonoplevaMarina Konopleva6,7*
  • 1Montefiore Medical Center, New York, United States
  • 2New York City Health and Hospitals Jacobi, New York, United States
  • 3The University of Texas MD Anderson Cancer Center Center for Cancer Immunology Research, Houston, United States
  • 4IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy
  • 5Universita degli Studi di Bologna, Bologna, Italy
  • 6Montefiore Einstein Medical Center, New York, United States
  • 7Albert Einstein College of Medicine, New York, United States

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TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent a biologically and clinically distinct subset of myeloid malignancies characterized by poor prognosis, resistance to standard therapies, and high rates of relapse. TP53 mutations, particularly biallelic are frequently associated with complex karyotypes and confer profound chemoresistance. Although hypomethylating agents and venetoclax-based combinations provide modest benefit, durable remissions remain rare. Novel therapeutic strategies targeting mutant p53, restoring wild-type function, or exploiting synthetic lethal pathways are under active investigation. This review aims to summarize current knowledge on the biology of TP53, prognostic implications, and therapeutic landscape of TP53-mutated AML/MDS, ongoing and past clinical trials in TP53-mutated AML/MDS patients, emphasizing the need for precision-guided, multimodal approaches to improve outcomes in this high-risk group.

Keywords: AML, Hypomethylating agents, mds, p53, TP53 mutation

Received: 30 Oct 2025; Accepted: 26 Jan 2026.

Copyright: © 2026 Deshpande, Li, Song, Forsberg, Cerchione, Martinelli and Konopleva. 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: Marina Konopleva

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material