Characterization of chromosome 5 aberrations in TP53 mutated myeloid neoplasms with ≥5% blasts: An International TP53 Investigators Network (iTiN) study
Recommended Citation
Yasin I, Stengel A, Shao H, Kaur A, Mason EF, Patwardhan PP, Bailey NG, Ghosh S, Inamdar KV, Patel AA, Pandiri M, Zhang J, Sojitra P, Tariq H, Pan Z, Wiredja D, Wang P, Tjota MY, Segal JP, Chang H, Sallman DA, Arber DA, Tefferi A, Badar T, Perry AM, Haferlach C, Lager AM, and Venkataraman G. Characterization of chromosome 5 aberrations in TP53 mutated myeloid neoplasms with ≥5% blasts: An International TP53 Investigators Network (iTiN) study. Cancer 2026;132(1):e70210.
Document Type
Article
Publication Date
1-1-2026
Publication Title
Cancer
Keywords
Humans, Female, Male, Middle Aged, Tumor Suppressor Protein p53, Aged, Mutation, Prognosis, Chromosomes, Human, Pair 5, Adult, Chromosome Aberrations, Hematopoietic Stem Cell Transplantation, Aged, 80 and over, Myelodysplastic Syndromes
Abstract
BACKGROUND: Isolated chromosome 5/5q losses (-5/5q) without TP53 mutations are associated with favorable outcomes in myeloid neoplasms (MN) with < 5% blasts. However, the clinical implication of concurrent -5/5q and TP53 aberrations in MN with ≥ 5% blasts is poorly understood.
METHODS: Patients with TP53-mutated MN carrying ≥ 5% blasts assessing the prognostic impact of -5/5q on 24-month overall survival (OS24) were examined.
RESULTS: Of 587 patients, 515 (88%) exhibited -5/5q overwhelmingly in the context of a complex karyotype (98.3% vs. 61.1% complex karyotype without -5/5q; p < .0001) and multihit TP53 allelic state (88.3% vs. 56.9%; p < .0001). Proportions of patients with blasts ≥ 20% were comparable between groups with and without -5/5q; p = 0.26. Notably, patients with -5/5q exhibited significantly fewer coalterations; p < .0001. Looking at outcomes, presence of -5/5q was associated with shorter median 24-month overall survival (7.8 months vs. 11.2 months; p(Log-rank) = .012), an effect restricted to subgroups with blasts < 20% (p = .039; N = 163), absent -7/7q (p = .007; N = 225), or WHO5-defined single hit allelic state (p = 0.030; N = 91). Importantly, -5/5q retained independent adverse prognostic significance regardless of TP53 allelic state in a multivariable model. Furthermore, among the subset of 75 (13%) patients undergoing allogeneic stem cell transplantation, -5/5q predicted significantly shorter median 5-year posttransplant survival (16.2 months vs. median not reached; p(Log-rank) = .009).
CONCLUSIONS: These findings emphasize the independent prognostic relevance of chromosome 5/5q losses underscoring the clinical relevance of cytogenetic testing for -5/5q even in this high-risk cohort.
Medical Subject Headings
Humans; Female; Male; Middle Aged; Tumor Suppressor Protein p53; Aged; Mutation; Prognosis; Chromosomes, Human, Pair 5; Adult; Chromosome Aberrations; Hematopoietic Stem Cell Transplantation; Aged, 80 and over; Myelodysplastic Syndromes
PubMed ID
41417597
Volume
132
Issue
1
First Page
70210
Last Page
70210
