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TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms

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 (TP53(mut)) MN. However, these assertions have not been specifically examined in therapy-relat...

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Detalles Bibliográficos
Autores principales: 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, Tefferi, Ayalew, Hiwase, Devendra K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090194/
https://www.ncbi.nlm.nih.gov/pubmed/37041128
http://dx.doi.org/10.1038/s41408-023-00821-x
Descripción
Sumario: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 (TP53(mut)) MN. However, these assertions have not been specifically examined in therapy-related myeloid neoplasm (t-MN), a subset enriched with TP53(mut). We analyzed 488 t-MN patients for TP53(mut). At least one TP53(mut) with variant allele frequency (VAF) ≥ 2% with or without loss of TP53 locus was noted in 182 (37.3%) patients and 88.2% of TP53(mut) t-MN had a VAF ≥10%. TP53(mut) t-MN with VAF ≥ 10% had a distinct clinical and biological profile compared to both TP53(mut) VAF < 10% and wild-type TP53 (TP53(wt)) cases. Notably, TP53(mut) VAF ≥ 10% had a significantly shorter survival compared to TP53(wt) (8.3 vs. 21.6 months; P < 0.001), while the survival of TP53(mut) VAF < 10% was comparable to TP53(wt). Within TP53(mut) VAF ≥ 10% cohort, the inferior outcomes persisted irrespective of the single- or multi-hit status, co-mutation pattern, or treatments received. Finally, survival of TP53(mut) patients was poor across all the blast categories and MDS patients with >10% blasts had inferior survival compared to <5%. In summary, TP53(mut) VAF ≥10% signified a clinically and molecularly homogenous cohort regardless of the allelic status.