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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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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
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author 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.
author_facet 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.
author_sort Shah, Mithun Vinod
collection PubMed
description 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.
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spelling pubmed-100901942023-04-13 TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms 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. Blood Cancer J Article 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. Nature Publishing Group UK 2023-04-11 /pmc/articles/PMC10090194/ /pubmed/37041128 http://dx.doi.org/10.1038/s41408-023-00821-x Text en © Crown 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
title TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
title_full TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
title_fullStr TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
title_full_unstemmed TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
title_short TP53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
title_sort tp53 mutation variant allele frequency of ≥10% is associated with poor prognosis in therapy-related myeloid neoplasms
topic Article
url 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
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