Citations 2
Characterization of chromosome 5 aberrations in TP53 mutated myeloid neoplasms with ≥5% blasts: An International TP53 Investigators Network (iTiN) study
Yasin, Irfan , Stengel, Anna , Shao, Haipeng , Kaur, Amandeep , Patwardhan, Pranav Pramod , Bailey, Nathanael G. , Inamdar, Kedar , Patel, Anand , Pandiri, M, Sojitra, Payal , Tariq, Hamza , Pan, Zenggang , Wiredja, Danica , Tjota, Melissa Y. , Segal, Jeremy , Chang, Hong , Sallman, David A. , Tefferi, Ayalew , Badar, Talha , Perry, Anamarija M. , Haferlach, Claudia, Patwardhan, Pranav P , Tefferi, Ayalew , Badar, Talha , Venkataraman, Girish , Patel, Anand , Shao, Haipeng, Mason, Emily F. , Ghosh, Sharmila , Zhang, Jingjing , Wang, Peng , Arber, Daniel A. , Haferlach, Claudia , Lager, Angela M.
Cancer | December 19, 2025 | Volume: 132 | Issue: 1 | Pages: No page available
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.
Karyotypic clonal fraction predicts adverse outcome in TP53 -mutated myeloid neoplasms: an International TP53 investigators Network (iTiN) study
Pandiri, M, Stengel, Anna , Shao, Haipeng , Velmurugan, S. , Jacob, Anisha, Symes, Emily , Kaur, Amandeep , Rojek, Alexandra E. , Sojitra, Payal , Wiredja, Danica , Chang, Hong , Patil, Esha, Patel, Jay , Patel, Ami B. , Pan, Zenggang , Findley, Anthony, Badar, Talha , Tariq, Hamza , Sallman, David A. , Bell, Robert , Perry, Anamarija M. , Fitzpatrick, Carrie , Pandiri, Madhavi , Zhou, Qianghua , Venkataraman, Girish , Badar, Talha , Rojek, Alexandra E , Zhang, Jingjing , Wang, Peng , Shao, Haipeng, Jacob, Anisha, Menon, Madhu P , Ghosh, Sharmila , Wool, Geoffrey D. , Arber, Daniel A. , Findley, Anthony, Haferlach, Claudia
Journal of Clinical Pathology | June 26, 2025 | Volume: 78 | Issue: 9 | Pages: 629-635
We investigated the prognostic impact of blast counts, TP53 allelic state determinants (number of hits, del(17p), variant allele frequency, complex karyotype),and a novel karyotypic clonal cell fraction (≤50% clonal cells vs >50% clonal cells (termed ‘CK50’)) in 495 individuals with TP53- mutated ( TP53 MUT ) myeloid neoplasms. Outcome examined was 24-month survival (OS24). The cohort (median age 71) included 29% (144/495) myelodysplastic syndromes (MDS)/MDS-acute myeloid leukaemia (AML) (1%–19% blasts) and 71% (351/495) AML (≥20% blasts), with 18% (81/460) having low CK50. Overall, 83% received front-line hypomethylating agents. Higher blast counts (<20% vs ≥20%) were marginally associated with CK50 (p=0.08). In the OS24 analysis, blast count showed a marginal association with OS24 (HR 1.3 (95% CI 1.0 to 1.6); p=0.07), while CK50 predicted significantly inferior outcomes (HR=1.7 (95% CI 1.2 to 2.3); p=0.002). In a multivariable model including all TP53 allelic state determinants, only CK50 and complex karyotype remained relevant for predicting adverse outcomes.