{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:41:54Z","timestamp":1790948514009,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"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":["American J Hematol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n The clinical relevance of\n TP53<\/jats:italic>\n mutations (\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n ) in myeloproliferative neoplasms (MPN) and their prognostic interaction with MPN subtype designation has not been systematically studied. In the current study, 114 patients with MPN harboring\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n (VAF\u2009\u2265\u20092%) were evaluated for overall survival (OS), calculated from the time of\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n detection: chronic phase myelofibrosis (MF\u2010CP;\n N<\/jats:italic>\n \u2009=\u200961); blast\u2010phase (MPN\u2010BP;\n N<\/jats:italic>\n \u2009=\u200931) or accelerated\u2010phase (MPN\u2010AP;\n N<\/jats:italic>\n \u2009=\u200916) MPN, and polycythemia vera\/essential thrombocythemia (PV\/ET;\n N<\/jats:italic>\n \u2009=\u20096). Sixty\u2010five (57%) patients harbored International Consensus Classification (ICC)\u2010defined multihit\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n and 56 (49%) monosomal\/complex karyotype (MK\/CK). Majority of MPN\u2010BP (90%) and MPN\u2010AP (81%) while 39% of MF\u2010CP and none of PV\/ET patients harbored multihit\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n . OS in MPN\u2010BP and MPN\u2010AP was equally dismal (median 6 vs. 4.5\u2009months, respectively;\n p<\/jats:italic>\n \u2009=\u20091.0), regardless of multihit configuration (\n p<\/jats:italic>\n \u2009=\u20090.44), while OS in\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n MPN\u2010BP\/AP (\n N<\/jats:italic>\n \u2009=\u200947; median 4\u2009months) was inferior to that of a separate cohort (\n N<\/jats:italic>\n \u2009=\u200949) with\n TP53<\/jats:italic>\n wild\u2010type MPN\u2010BP\/AP (median 11\u2009months;\n p<\/jats:italic>\n \u2009<\u20090.01). OS in MF\u2010CP was significantly shorter with multihit versus non\u2010multihit\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n (median 10 vs. 35\u2009months; HR 2.9;\n p<\/jats:italic>\n \u2009<\u20090.01), independent of other MF\u2010relevant genetic risk factors, including\n ASXL1\/SRSF2\/U2AF1<\/jats:italic>\n mutations. Multihit\n TP53<\/jats:italic>\n \n MUT<\/jats:italic>\n <\/jats:sup>\n was also associated with inferior survival following allogeneic stem cell transplant (ASCT): median 9\u2009months versus \u201cnot reached\u201d in patients with (\n N<\/jats:italic>\n \u2009=\u20099) versus without (\n N<\/jats:italic>\n \u2009=\u20098) multihit\n TP53<\/jats:italic>\n MUT<\/jats:sup>\n (\n p<\/jats:italic>\n \u2009<\u20090.01). The presence of multihit or non\u2010multihit\n TP53<\/jats:italic>\n MUT<\/jats:sup>\n in MPN\u2010BP\/AP or multihit\n TP53<\/jats:italic>\n MUT<\/jats:sup>\n in MF\u2010CP is associated with exceptionally poor prognosis and justifies inclusion into the ICC category of \u201cmyeloid neoplasms with mutated\n TP53<\/jats:italic>\n .\u201d By contrast, detection of non\u2010multihit\n TP53<\/jats:italic>\n MUT<\/jats:sup>\n , by itself, might not endanger short\u2010term survival in MF\u2010CP, PV, or ET.\n <\/jats:p>","DOI":"10.1002\/ajh.27609","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T05:25:16Z","timestamp":1738041916000},"page":"552-560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["\n TP53<\/i>\n <\/scp>\n Mutations in Myeloproliferative Neoplasms: Context\u2010Dependent Evaluation of Prognostic Relevance"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"first","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maymona","family":"Abdelmagid","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6241-1206","authenticated-orcid":false,"given":"Giuseppe G.","family":"Loscocco","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota USA"},{"name":"CRIMM, Center Research and Innovation of Myeloproliferative Neoplasms, University of Florence, AOU Careggi Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saubia","family":"Fathima","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2730-8593","authenticated-orcid":false,"given":"Kebede H.","family":"Begna","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-3715","authenticated-orcid":false,"given":"Aref","family":"Al\u2010Kali","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Foran","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Jacksonville Florida 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-7013","authenticated-orcid":false,"given":"Attilio","family":"Orazi","sequence":"additional","affiliation":[{"name":"Department of Pathology Texas Tech University Health Sciences Center El Paso Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2160-9689","authenticated-orcid":false,"given":"Daniel A.","family":"Arber","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9084-4148","authenticated-orcid":false,"given":"Animesh","family":"Pardanani","sequence":"additional","affiliation":[{"name":"Division of Hematology Mayo Clinic Rochester Minnesota 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