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- Title
TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms.
- Authors
Shah, Mithun Vinod; Tran, Elizabeth Ngoc Hoa; Shah, Syed; Chhetri, Rakchha; Baranwal, Anmol; Ladon, Dariusz; Shultz, Carl; Al-Kali, Aref; Brown, Anna L.; Chen, Dong; Scott, Hamish S.; Greipp, Patricia; Thomas, Daniel; Alkhateeb, Hassan B.; Singhal, Deepak; Gangat, Naseema; Kumar, Sharad; Patnaik, Mrinal M.; Hahn, Christopher N.; Kok, Chung Hoow
- Abstract
Revised diagnostic criteria for myeloid neoplasms (MN) issued by the International Consensus Classification (ICC) and the World Health Organization (WHO) recommended major change pertaining to TP53-mutated (TP53mut) MN. However, these assertions have not been specifically examined in therapy-related myeloid neoplasm (t-MN), a subset enriched with TP53mut. We analyzed 488 t-MN patients for TP53mut. At least one TP53mut with variant allele frequency (VAF) ≥ 2% with or without loss of TP53 locus was noted in 182 (37.3%) patients and 88.2% of TP53mut t-MN had a VAF ≥10%. TP53mut t-MN with VAF ≥ 10% had a distinct clinical and biological profile compared to both TP53mut VAF < 10% and wild-type TP53 (TP53wt) cases. Notably, TP53mut VAF ≥ 10% had a significantly shorter survival compared to TP53wt (8.3 vs. 21.6 months; P < 0.001), while the survival of TP53mut VAF < 10% was comparable to TP53wt. Within TP53mut VAF ≥ 10% cohort, the inferior outcomes persisted irrespective of the single- or multi-hit status, co-mutation pattern, or treatments received. Finally, survival of TP53mut patients was poor across all the blast categories and MDS patients with >10% blasts had inferior survival compared to <5%. In summary, TP53mut VAF ≥10% signified a clinically and molecularly homogenous cohort regardless of the allelic status.
- Subjects
WORLD Health Organization; GENE frequency; TUMORS; GENETIC mutation; PROGNOSIS
- Publication
Blood Cancer Journal, 2023, Vol 13, Issue 1, p1
- ISSN
2044-5385
- Publication type
Article
- DOI
10.1038/s41408-023-00821-x