Citations 2
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.
Somatic co‐alteration signatures are prognostic in high‐grade TP53‐mutated myeloid neoplasms
Symes, Emily , Sojitra, Payal , Patel, Anand , Hasan, Faheema , Zhou, Qianghua , Findley, Anthony, Badar, Talha , Tariq, Hamza , Chang, Hong , Bell, Robert , Perry, Anamarija M. , Menon, Madhu P , Patel, Anand , Badar, Talha , Tariq, Hamza , Chang, Hong , Perry, Anamarija M , Venkataraman, Girish , Zhou, Qianghua , Wang, Peng , Ghosh, Sharmila , Roloff, Gregory W. , Findley, Anthony, Zhang, Jingjing
British Journal of Haematology | November 18, 2024 | Volume: 206 | Issue: 4 | Pages: 1103-1108
SummaryTo assess the relevance of co‐occurring somatic mutations in TP53‐mutated myeloid neoplasms with ≥10% blasts, we pooled 325 individuals from 10 centres. We focused on comparing three published somatic co‐alteration signatures comprising (1) nine MDS‐related genes (‘ICC‐MDSR’), (2) ICC‐MDSR + additional secondary mutations‐related genes (‘Tazi signature’) and (3) EPI6 (comprising six genes). Outcomes examined were 24‐month overall survival (OS24) and front‐line complete response (CR1). The median age was 69 years with 77% receiving front‐line hypomethylating agents (HMA). All three signatures ICC‐MDSR (p = 0.009), Tazi signature (p = 0.001) and EPI6 (p = 0.025) predicted inferior CR1. In the low‐intensity (HMA) subgroup, only Tazi signature (p = 0.026) predicted inferior CR1. In OS24 analysis of the HMA‐treated subgroup (N = 200), only Tazi signature was adverse (hazard ratio, HR = 1.6 [1.1–2.2]; p = 0.011). However, a forward stepwise multivariable age‐adjusted Cox model including all three signatures picked EPI6 as the sole significant adverse predictor in the entire cohort (p = 0.0001) as well as within the HMA‐treated subgroup (p = 0.0071). These data confirm the value of testing co‐occurring somatic alterations even within a high‐grade TP53‐mutated myeloid neoplasm cohort.