{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:22:15Z","timestamp":1789593735297,"version":"build-2803163510"},"reference-count":153,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["K08HL168777"],"award-info":[{"award-number":["K08HL168777"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leukemia Research Foundation New Investigator Research Grant Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) comprise a distinct subgroup of myeloid neoplasms with unique biological and clinical features. The molecular alterations linked to TP53 mutations drive genomic instability and treatment resistance and ultimately lead to poor survival outcomes. The disease biology is further shaped by alterations in immune response within the bone marrow microenvironment and significant changes in cellular metabolism. Conventional treatments, including chemotherapy and hypomethylating agents +\/\u2212 venetoclax, offer limited benefit, with high relapse rates and short remissions. Allogeneic bone marrow transplantation is the only curative approach, but the vast majority of patients relapse. Novel therapeutic approaches\u2014ranging from p53 reactivation strategies to immunotherapy and targeted inhibition of specific signaling pathways\u2014are under active investigation. Our review summarizes current knowledge on the molecular pathogenesis, prognostic implications, and therapeutic landscape of TP53-mutated MDS\/AML and discusses ongoing challenges and opportunities for improving patient outcomes.<\/jats:p>","DOI":"10.3390\/ijms262210818","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T10:56:45Z","timestamp":1762513005000},"page":"10818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular and Clinical Insights into TP53-Mutated MDS and AML"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7377-0930","authenticated-orcid":false,"given":"Erotokritos","family":"Georgantzinos","sequence":"first","affiliation":[{"name":"Division of Hematological Malignancies, Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6792-8298","authenticated-orcid":false,"given":"Theodoros","family":"Karantanos","sequence":"additional","affiliation":[{"name":"Division of Hematological Malignancies, Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/358015a0","article-title":"P53, Guardian of the Genome","volume":"358","author":"Lane","year":"1992","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1182\/blood.V84.9.3148.3148","article-title":"P53 Mutations Are Associated with Resistance to Chemotherapy and Short Survival in Hematologic Malignancies","volume":"84","author":"Wattel","year":"1994","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zawacka, J.E. 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