{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:21:21Z","timestamp":1783606881275,"version":"3.55.0"},"reference-count":187,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fonc.2026.1735418","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T05:28:13Z","timestamp":1771824493000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches"],"prefix":"10.3389","volume":"16","author":[{"given":"Shweta","family":"Deshpande","sequence":"first","affiliation":[{"name":"Department of Oncology, Montefiore Einstein Comprehensive Cancer Center","place":["Bronx, NY, United 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