Characterization of chromosome 5 aberrations in TP53 mutated myeloid neoplasms with ≥5% blasts: An International TP53 Investigators Network (iTiN) study

作者：Irfan Yasin, Anna Stengel, Haipeng Shao, Amandeep Kaur, Emily F. Mason, Pranav Pramod Patwardhan, Nathanael G. Bailey, Sharmila Ghosh, Kedar Inamdar, Anand Patel, M Pandiri, Jingjing Zhang, Payal Sojitra, Hamza Tariq, Zenggang Pan, Danica Wiredja, Peng Wang, Melissa Y. Tjota, Jeremy Segal, Hong Chang, David A. Sallman, Daniel A. Arber, Ayalew Tefferi, Talha Badar, Anamarija M. Perry, Claudia Haferlach, Angela M. Lager, Girish Venkataraman · 发表于：Cancer · 年份：2025 · DOI：10.1002/cncr.70210 · 被引用次数：1 · 研究领域：Acute Myeloid Leukemia Research、Chronic Myeloid Leukemia Treatments、Cancer-related Molecular Pathways

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...