{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:56:53Z","timestamp":1755223013099,"version":"3.43.0"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Patients with <jats:italic>TP53<\/jats:italic> mutations in acute myeloid leukemia (AML) and blast phase myeloproliferative neoplasms (MPN\u2010BP) experience similar poor clinical outcomes. A retrospective analysis of 39 patients with <jats:italic>TP53<\/jats:italic> mutations (23 with AML and 16 with MPN\u2010BP) revealed comparable mutation patterns associated with prognostic significance. A total of 47 distinct <jats:italic>TP53<\/jats:italic> mutations were identified, including seven patients with multiple mutations. Based on clinical outcomes, we propose a two\u2010tiered risk stratification for <jats:italic>TP53<\/jats:italic>\u2010mutated AML and MPN\u2010BP. The high\u2010risk group mutations, such as splice site variants in Intron 4 (especially c.376), missense mutations in Exon 5 (notably p.R175H), and mutations in the oligomerization domain (OD), were associated with, particularly, worse overall survival (OS\u2009&lt;\u20093\u2009months). Conversely, single missense mutations in Exons 6 and 7 (notably p.Y220C, p.R248N, p.R248Q, and p.R248W), and mutations in the transactivation domain (TAD), constituted a low\u2010risk group and were associated with relatively better prognosis (median OS: 10.15\u2009months for the low\u2010risk group vs. 1.3\u2009months for the high\u2010risk group, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). These findings support the hypothesis that distinct <jats:italic>TP53<\/jats:italic> mutations can lead to varying cellular effects, therapeutic responses, and clinical outcomes. Consequently, acute myeloid neoplasms (AML and MPN\u2010BP) harboring certain <jats:italic>TP53<\/jats:italic> mutations may exhibit increased aggressiveness compared to other <jats:italic>TP53<\/jats:italic> mutants, underscoring the need for prioritized clinical research and therapeutic targeting.<\/jats:p>","DOI":"10.1111\/ejh.14421","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T18:16:16Z","timestamp":1743358576000},"page":"57-63","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp><i>TP53<\/i><\/scp>\u2010Mutated Acute Myeloid Leukemia and Blast Phase Myeloproliferative Neoplasm: Distinct Mutation Leads to Poorer Prognosis"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-9410","authenticated-orcid":false,"given":"Dong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Connecticut  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6287-4569","authenticated-orcid":false,"given":"Miguel","family":"Cantu","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2372-3653","authenticated-orcid":false,"given":"Alexa","family":"Siddon","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Yale School of Medicine  New Haven Connecticut USA"},{"name":"Department of Pathology Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga K.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.180"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01413-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014472"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.151"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015850"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006239"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.14280"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01613-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-00989-y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13164088"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-024-06054-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-21-0583"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-019-0141-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.642603"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2019.12.015"}],"container-title":["European Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejh.14421","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:30:25Z","timestamp":1754904625000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejh.14421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/ejh.14421"],"URL":"https:\/\/doi.org\/10.1111\/ejh.14421","archive":["Portico"],"relation":{},"ISSN":["0902-4441","1600-0609"],"issn-type":[{"type":"print","value":"0902-4441"},{"type":"electronic","value":"1600-0609"}],"subject":[],"published":{"date-parts":[[2025,3,28]]},"assertion":[{"value":"2025-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}