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Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma

Adult T‐cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion‐deletions (SNVs/indels) of the TP53 gene in 37 ind...

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Autores principales: Sakamoto, Yuma, Ishida, Takashi, Masaki, Ayako, Murase, Takayuki, Takeshita, Morishige, Muto, Reiji, Iwasaki, Hiromi, Ito, Asahi, Kusumoto, Shigeru, Nakano, Nobuaki, Tokunaga, Masahito, Yonekura, Kentaro, Tashiro, Yukie, Iida, Shinsuke, Utsunomiya, Atae, Ueda, Ryuzo, Inagaki, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291095/
https://www.ncbi.nlm.nih.gov/pubmed/34405395
http://dx.doi.org/10.1111/bjh.17749
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author Sakamoto, Yuma
Ishida, Takashi
Masaki, Ayako
Murase, Takayuki
Takeshita, Morishige
Muto, Reiji
Iwasaki, Hiromi
Ito, Asahi
Kusumoto, Shigeru
Nakano, Nobuaki
Tokunaga, Masahito
Yonekura, Kentaro
Tashiro, Yukie
Iida, Shinsuke
Utsunomiya, Atae
Ueda, Ryuzo
Inagaki, Hiroshi
author_facet Sakamoto, Yuma
Ishida, Takashi
Masaki, Ayako
Murase, Takayuki
Takeshita, Morishige
Muto, Reiji
Iwasaki, Hiromi
Ito, Asahi
Kusumoto, Shigeru
Nakano, Nobuaki
Tokunaga, Masahito
Yonekura, Kentaro
Tashiro, Yukie
Iida, Shinsuke
Utsunomiya, Atae
Ueda, Ryuzo
Inagaki, Hiroshi
author_sort Sakamoto, Yuma
collection PubMed
description Adult T‐cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion‐deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required.
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spelling pubmed-92910952022-07-20 Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma Sakamoto, Yuma Ishida, Takashi Masaki, Ayako Murase, Takayuki Takeshita, Morishige Muto, Reiji Iwasaki, Hiromi Ito, Asahi Kusumoto, Shigeru Nakano, Nobuaki Tokunaga, Masahito Yonekura, Kentaro Tashiro, Yukie Iida, Shinsuke Utsunomiya, Atae Ueda, Ryuzo Inagaki, Hiroshi Br J Haematol Haematological malignancy–Clinical Adult T‐cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion‐deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required. John Wiley and Sons Inc. 2021-08-17 2021-11 /pmc/articles/PMC9291095/ /pubmed/34405395 http://dx.doi.org/10.1111/bjh.17749 Text en © 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Haematological malignancy–Clinical
Sakamoto, Yuma
Ishida, Takashi
Masaki, Ayako
Murase, Takayuki
Takeshita, Morishige
Muto, Reiji
Iwasaki, Hiromi
Ito, Asahi
Kusumoto, Shigeru
Nakano, Nobuaki
Tokunaga, Masahito
Yonekura, Kentaro
Tashiro, Yukie
Iida, Shinsuke
Utsunomiya, Atae
Ueda, Ryuzo
Inagaki, Hiroshi
Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma
title Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma
title_full Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma
title_fullStr Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma
title_full_unstemmed Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma
title_short Clinical significance of TP53 mutations in adult T‐cell leukemia/lymphoma
title_sort clinical significance of tp53 mutations in adult t‐cell leukemia/lymphoma
topic Haematological malignancy–Clinical
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291095/
https://www.ncbi.nlm.nih.gov/pubmed/34405395
http://dx.doi.org/10.1111/bjh.17749
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