Evidence-based risk stratification of myeloid neoplasms harboring TP53 mutations

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dc.contributor.authorShah, M.V.
dc.contributor.authorHung, K.
dc.contributor.authorBaranwal, A.
dc.contributor.authorKutyna, M.M.
dc.contributor.authorAl-Kali, A.
dc.contributor.authorToop, C.
dc.contributor.authorGreipp, P.T.
dc.contributor.authorBrown, A.L.
dc.contributor.authorShah, S.N.
dc.contributor.authorKhanna, S.
dc.contributor.authorLadon, D.
dc.contributor.authorGannamani, V.
dc.contributor.authorChen, D.
dc.contributor.authorBegna, K.
dc.contributor.authorPrice, Z.
dc.contributor.authorRud, D.
dc.contributor.authorLitzow, M.R.
dc.contributor.authorHogan, W.J.
dc.contributor.authorBardy, P.G.
dc.contributor.authorBadar, T.
dc.contributor.authoret al.
dc.date.issued2025
dc.description.abstractThis retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53(mut)) myeloid neoplasms (MNs). Of 580 MNs harboring TP53(mut) with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53(mut) AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53(mut) MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.
dc.description.statementofresponsibilityMithun Vinod Shah, Kevin Hung, Anmol Baranwal, Monika M. Kutyna, Aref Al-Kali, Carla Toop, Patricia Greipp, Anna Brown, Syed Shah, Shreyas Khanna, Dariusz Ladon, Vedavyas Gannamani, Dong Chen, Kebede Begna, Zoe K. Price, Danielle Rud, Mark R. Litzow, William J. Hogan, Peter Bardy, Talha Badar, Sharad Kumar, David T. Yeung, Mrinal M. Patnaik, James M. Foran, Rong He, Naseema Gangat, Hamish S. Scott, Cecilia Y. Arana Yi, Hassan Alkhateeb, Abhishek A. Mangaonkar, Daniel Thomas, -, Christopher N. Hahn, Attilio Orazi, Daniel A. Arber, Chung Hoow Kok, Ayalew Tefferi, and Devendra Hiwase
dc.identifier.citationBlood advances, 2025; 9(13):3370-3380
dc.identifier.doi10.1182/bloodadvances.2024015238
dc.identifier.issn2473-9529
dc.identifier.issn2473-9537
dc.identifier.orcidKutyna, M.M. [0000-0003-2315-091X]
dc.identifier.orcidBrown, A.L. [0000-0002-9023-0138]
dc.identifier.orcidPrice, Z. [0000-0001-5306-3468]
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.orcidYeung, D.T. [0000-0002-7558-9927]
dc.identifier.orcidScott, H.S. [0000-0002-5813-631X]
dc.identifier.orcidHahn, C.N. [0000-0001-5105-2554]
dc.identifier.orcidKok, C.H. [0000-0002-3181-7852]
dc.identifier.orcidHiwase, D.K. [0000-0002-6666-3056]
dc.identifier.urihttps://hdl.handle.net/2440/147730
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1195517
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT2007739
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT2029809
dc.rights© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
dc.source.urihttps://doi.org/10.1182/bloodadvances.2024015238
dc.subjectMyeloid Neoplasia
dc.subject.meshHumans
dc.subject.meshMyelodysplastic Syndromes
dc.subject.meshPrognosis
dc.subject.meshRisk Assessment
dc.subject.meshRetrospective Studies
dc.subject.meshGene Frequency
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.subject.meshLeukemia, Myeloid, Acute
dc.titleEvidence-based risk stratification of myeloid neoplasms harboring TP53 mutations
dc.typeJournal article
pubs.publication-statusPublished online

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