TP53 Mutations in Myeloproliferative Neoplasms: Context-Dependent Evaluation of Prognostic Relevance

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dc.contributor.authorTefferi, A.
dc.contributor.authorAbdelmagid, M.
dc.contributor.authorLoscocco, G.G.
dc.contributor.authorFathima, S.
dc.contributor.authorBegna, K.H.
dc.contributor.authorAl-Kali, A.
dc.contributor.authorForan, J.
dc.contributor.authorPalmer, J.
dc.contributor.authorBadar, T.
dc.contributor.authorPatnaik, M.M.
dc.contributor.authorReichard, K.K.
dc.contributor.authorHe, R.
dc.contributor.authorZepeda Mendoza, C.J.
dc.contributor.authorShah, M.
dc.contributor.authorOrazi, A.
dc.contributor.authorArber, D.A.
dc.contributor.authorPardanani, A.
dc.contributor.authorVannucchi, A.M.
dc.contributor.authorHiwase, D.
dc.contributor.authorGangat, N.
dc.contributor.authoret al.
dc.date.issued2025
dc.description.abstractThe clinical relevance of TP53 mutations (TP53 MUT ) 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 TP53 MUT (VAF ≥ 2%) were evaluated for overall survival (OS), calculated from the time of TP53 MUT detection: chronic phase myelofibrosis (MF-CP; N = 61); blast-phase (MPN-BP; N = 31) or accelerated-phase (MPN-AP; N = 16) MPN, and polycythemia vera/essential thrombocythemia (PV/ET; N = 6). Sixty-five (57%) patients harbored International Consensus Classification (ICC)-defined multihit TP53 MUT and 56 (49%) monosomal/complex karyotype (MK/CK). Majority of MPN-BP (90%) and MPN-AP (81%) while 39% of MF-CP and none of PV/ET patients harbored multihit TP53 MUT . OS in MPN-BP and MPN-AP was equally dismal (median 6 vs. 4.5 months, respectively; p = 1.0), regardless of multihit configuration (p = 0.44), while OS in TP53 MUT MPN-BP/AP (N = 47; median 4 months) was inferior to that of a separate cohort (N = 49) with TP53 wild-type MPN-BP/AP (median 11 months; p < 0.01). OS in MF-CP was significantly shorter with multihit versus non-multihit TP53 MUT (median 10 vs. 35 months; HR 2.9; p < 0.01), independent of other MF-relevant genetic risk factors, including ASXL1/SRSF2/U2AF1 mutations. Multihit TP53 MUT was also associated with inferior survival following allogeneic stem cell transplant (ASCT): median 9 months versus “not reached” in patients with (N = 9) versus without (N = 8) multihit TP53 MUT (p < 0.01). The presence of multihit or non-multihit TP53 MUT in MPN-BP/AP or multihit TP53 MUT in MF-CP is associated with exceptionally poor prognosis and justifies inclusion into the ICC category of “myeloid neoplasms with mutated TP53.” By contrast, detection of non-multihit TP53 MUT, by itself, might not endanger short-term survival in MF-CP, PV, or ET.
dc.description.statementofresponsibilityAyalew Tefferi, Maymona Abdelmagid, Giuseppe G. Loscocco, Saubia Fathima, Kebede H. Begna, Aref Al-Kali, James Foran, Jeanne Palmer, Talha Badar, Mrinal M. Patnaik, Kaaren K. Reichard, Rong He, Cinthya J. Zepeda Mendoza, Mithun Shah, Attilio Orazi, Daniel A. Arber, Animesh Pardanani, Alessandro M. Vannucchi, Devendra Hiwase, Naseema Gangat, Paola Guglielmelli
dc.identifier.citationAmerican Journal of Hematology, 2025; 100(4):552-560
dc.identifier.doi10.1002/ajh.27609
dc.identifier.issn0361-8609
dc.identifier.issn1096-8652
dc.identifier.orcidHiwase, D. [0000-0002-6666-3056]
dc.identifier.urihttps://hdl.handle.net/2440/145994
dc.language.isoen
dc.publisherWiley
dc.relation.grantNHMRC
dc.rights© 2025 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
dc.source.urihttps://doi.org/10.1002/ajh.27609
dc.subjectICC
dc.subjectkaryotype
dc.subjectprognosis
dc.subjectsurvival
dc.subjectWHO
dc.subject.meshHumans
dc.subject.meshMyeloproliferative Disorders
dc.subject.meshPrognosis
dc.subject.meshMutation
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshMiddle Aged
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshTumor Suppressor Protein p53
dc.titleTP53 Mutations in Myeloproliferative Neoplasms: Context-Dependent Evaluation of Prognostic Relevance
dc.typeJournal article
pubs.publication-statusPublished

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