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Multicenter Study
. 2025 Aug 18;78(9):629-635.
doi: 10.1136/jcp-2024-209954.

Karyotypic clonal fraction predicts adverse outcome in TP53-mutated myeloid neoplasms: an International TP53 investigators Network (iTiN) study

Madhavi Pandiri #  1 , Anna Stengel #  2 , Jingjing Zhang  3 , Peng Wang  4 , Haipeng Shao  5 , Sinthujaa Velmurugan  4 , Anisha Jacob  4 , Emily Symes  4 , Amandeep Kaur  6 , Alexandra Rojek  4 , Payal Sojitra  7 , Danica Wiredja  3 , Qianghua Zhou  8 , Hong Chang  8 , Esha Patil  4 , Jay L Patel  9 , Ami B Patel  9 , Madhu Menon  9 , Sharmila Ghosh  10 , Geoffrey D Wool  4 , Daniel A Arber  4 , Zenggang Pan  3 , Anthony Findley  11 , Talha Badar  11 , Hamza Tariq  12 , David Sallman  5 , Robert C Bell  13 , Anamarija Perry  13 , Claudia Haferlach  2 , Carrie Fitzpatrick  4 , Girish Venkataraman  1
Affiliations
Multicenter Study

Karyotypic clonal fraction predicts adverse outcome in TP53-mutated myeloid neoplasms: an International TP53 investigators Network (iTiN) study

Madhavi Pandiri et al. J Clin Pathol. .

Abstract

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.

Keywords: BONE MARROW; CYTOGENETICS; Genes, p53; Myelodysplastic Syndromes; Pathology, Molecular.

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Conflict of interest statement

Competing interests: DS reports research funding from Aprea Therapeutics and Jazz Pharmaceuticals. DS reports consulting and/or other fees from Abbvie, Agios, Akesobio Avencell Europe GmbH, Bluebird Bio, BMS, Curis, Gilead Sciences, Incyte, Intellia Therapeutics, Janssen Global Services, Jazz Pharmaceuticals, Kite Pharma, Molecular Partners AG, Novartis, Servier Pharmaceuticals, Shattuck Labs, Syndax Pharmaceuticals, Syros Pharmaceuticals, and Takeda Pharmaceutical. MS reports serving on advisory board for Novartis, Kymera, Sierra Oncology, GSK, Rigel, BMS, Sobi and Syndax; CH, Part ownership of MLL Münchner Leukämielabor. MP, AS, JZ, PW, HS, SV, AJ, ES, AK, AR, PS, DW, QZ, HC, EP, JLP, ABP, MM, SG, GDW, DAA, ZP, AF, TB, HT, RCB, AP, CF and GV: no disclosure(s).

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