Journal of clinical pathology · 2025
Karyotypic clonal fraction predicts adverse outcome in TP53-mutated myeloid neoplasms: an International TP53 investigators Network (iTiN) study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Pandiri Madhavi, Stengel Anna, Zhang Jingjing, Wang Peng, Shao Haipeng, Velmurugan Sinthujaa, Jacob Anisha, Symes Emily, Kaur Amandeep, Rojek Alexandra, Sojitra Payal, Wiredja Danica, Zhou Qianghua, Chang Hong, Patil Esha, Patel Jay L, Patel Ami B, Menon Madhu, Ghosh Sharmila, Wool Geoffrey D, Arber Daniel A, Pan Zenggang, Findley Anthony, Badar Talha, Tariq Hamza, Sallman David, Bell Robert C, Perry Anamarija, Haferlach Claudia, Fitzpatrick Carrie, Venkataraman Girish
Аннотация
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 (TP53MUT ) 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.