{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T07:00:39Z","timestamp":1789887639475,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008321","name":"Pennsylvania State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n TP53<\/jats:italic>\n mutations (\n TP53<\/jats:italic>\n m) are uncommon in chronic\u2010phase Ph\u2013negative myeloproliferative neoplasms but become enriched in myelofibrosis (MF) and accelerated\/blast phase myeloproliferative (AP\/BP\u2010MPN). Their prevalence, allelic distribution, and phase\u2010stratified outcomes have not been systematically synthesized.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A PRISMA\u2010guided systematic review of EMBASE and PubMed identified cohort studies of adult Ph\u2013negative MPN with molecularly confirmed\n TP53<\/jats:italic>\n m. Pooled proportions with 95% CI were generated using random\u2010effects models; survival outcomes were summarized descriptively.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Eleven retrospective cohort studies (\n N<\/jats:italic>\n = \u2009603) met inclusion criteria.\n TP53<\/jats:italic>\n m were uncommon overall (3%, 95% CI: 1\u201313;\n I<\/jats:italic>\n 2<\/jats:sup>\n = \u200997%) but substantially enriched in MF or AP\/BP\u2010MPN cohorts (10%, 95% CI: 4\u201324;\n I<\/jats:italic>\n 2<\/jats:sup>\n = \u200989%). Among\n TP53<\/jats:italic>\n m patients, disease distribution included AP\/BP\u2010MPN (33%, 95% CI: 26\u201341), MF (31%, 95% CI: 15\u201354), ET (16%, 95% CI: 5\u201341), and PV (11%, 95% CI: 4\u201327). Single\u2010 and multi\u2010hit\n TP53<\/jats:italic>\n were present in comparable proportions (52%\u00a0vs. 48%), with a pooled mean VAF of 37.48% (95% CI: 30.73\u201344.24;\n I<\/jats:italic>\n 2<\/jats:sup>\n = \u200997%). Unfavorable karyotype was identified in 42%. Median OS was: 37.4\u201372 months in PV, 44.4\u201354.6 months in ET, 11.6\u201324.7 months in MF, and 4.5\u20136 months in AP\/BP\u2010MPN. In CP\u2010MPN, multi\u2010hit\n TP53<\/jats:italic>\n conferred worse OS (9.5\u201318.5 months) versus single\u2010hit disease (38 months to not reached); this distinction was absent in AP\/BP\u2010MPN. Leukemic transformation occurred in 35% (95% CI: 16\u201360;\n I<\/jats:italic>\n 2<\/jats:sup>\n = \u200993%) across two reporting cohorts, and allo\u2010HCT was utilized in only 16% (95% CI: 13\u201319;\n I<\/jats:italic>\n 2<\/jats:sup>\n = \u200912%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n TP53<\/jats:italic>\n m Ph\u2013negative MPN are enriched in advanced\u2010phase disease, carry comparable proportions of single\u2010hit and multi\u2010hit allelic configurations with high clonal burden, and demonstrate a clinically important survival gradient. Allelic status is a key prognostic determinant in CP\u2010MPN but loses significance in AP\/BP\u2010MPN where outcomes are uniformly dismal. Standardized molecular reporting and prospective clinical trials are needed.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n The authors have confirmed clinical trial registration is not needed for this submission.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jha2.70385","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:09:38Z","timestamp":1789884578000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinicopathologic Characteristics of Somatic\n TP53<\/i>\n Mutations in Philadelphia Chromosome\u2013Negative Myeloproliferative Neoplasms: A Systematic Review"],"prefix":"10.1002","volume":"7","author":[{"given":"Mahmood","family":"Aldapt","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology Mayo Clinic Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Kaddoura","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Heart Hospital Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed O.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Unity Hospital\/Rochester Regional Health Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Najim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Penn State \u2013 M.S. Hershey Medical Center Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Salem","sequence":"additional","affiliation":[{"name":"Division of Hospital Medicine The Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman F.","family":"Al\u2010Mashdali","sequence":"additional","affiliation":[{"name":"Department of Hematology National Center for Cancer Care and Research Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassam","family":"Muthanna","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Missouri Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruba Adel","family":"Aweer","sequence":"additional","affiliation":[{"name":"College of Medicine Qatar University Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marrita","family":"Rabadi","sequence":"additional","affiliation":[{"name":"College of Medicine Qatar University Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehab F.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Hematology National Center for Cancer Care and Research Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17193142"},{"issue":"4","key":"e_1_2_12_3_1","first-page":"863","article-title":"Pathogenesis and Management of High Molecular Risk Myeloproliferative Neoplasms","volume":"110","author":"VY 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