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RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD

Adult T‐cell acute lymphoblastic leukemia (T‐ALL) is a heterogeneous group of acute leukemias that account for about one third of all cases of Philadelphia chromosome (Ph)‐negative ALL. Recently, a molecular classifier using the mutational status of NOTCH1, FBXW7, RAS, and PTEN (NFRP) has been shown...

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Autores principales: Sakhdari, Ali, Thakral, Beenu, Loghavi, Sanam, Kanagal‐Shamanna, Rashmi, Yin, C. Cameron, Zuo, Zhuang, Routbort, Mark J., Luthra, Rajyalakshmi, Medeiros, L. Jeffrey, Wang, Sa A., Patel, Keyur P., Ok, Chi Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997098/
https://www.ncbi.nlm.nih.gov/pubmed/31804006
http://dx.doi.org/10.1002/cam4.2757
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author Sakhdari, Ali
Thakral, Beenu
Loghavi, Sanam
Kanagal‐Shamanna, Rashmi
Yin, C. Cameron
Zuo, Zhuang
Routbort, Mark J.
Luthra, Rajyalakshmi
Medeiros, L. Jeffrey
Wang, Sa A.
Patel, Keyur P.
Ok, Chi Young
author_facet Sakhdari, Ali
Thakral, Beenu
Loghavi, Sanam
Kanagal‐Shamanna, Rashmi
Yin, C. Cameron
Zuo, Zhuang
Routbort, Mark J.
Luthra, Rajyalakshmi
Medeiros, L. Jeffrey
Wang, Sa A.
Patel, Keyur P.
Ok, Chi Young
author_sort Sakhdari, Ali
collection PubMed
description Adult T‐cell acute lymphoblastic leukemia (T‐ALL) is a heterogeneous group of acute leukemias that account for about one third of all cases of Philadelphia chromosome (Ph)‐negative ALL. Recently, a molecular classifier using the mutational status of NOTCH1, FBXW7, RAS, and PTEN (NFRP) has been shown to distinguish low‐ vs high‐risk groups in adult T‐ALL patients treated using the Berlin‐Frankfurt‐Münster ALL protocol. However, it is unknown if this molecular classifier can stratify adult T‐ALL patients treated with hyper‐CVAD ± nelarabine. We identified a relatively small cohort of 27 adults with T‐ALL who were uniformly treated with hyper‐CVAD ± nelarabine with available mutational analysis at time of diagnosis. The most commonly mutated genes in this group were NOTCH1 (52%), NRAS (22%), DNMT3A (19%), KRAS (15%), and TP53 (7%). The NFRP molecular classifier failed to stratify overall survival (OS; P = .84) and relapse‐free survival (RFS; P = .18) in this cohort. We developed a new stratification model combining K/NRAS and TP53 mutations as high‐risk factors and showed that mutations in these genes predicted poorer OS (P = .03) and RFS (P = .04). While the current study is limited by cohort size, these data suggest that the NFRP molecular classifier might not be applicable to adult T‐ALL patients treated with hyper‐CVAD ± nelarabine. RAS/TP53 mutation status, however, was useful in risk stratification in adults with T‐ALL.
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spelling pubmed-69970982020-02-05 RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD Sakhdari, Ali Thakral, Beenu Loghavi, Sanam Kanagal‐Shamanna, Rashmi Yin, C. Cameron Zuo, Zhuang Routbort, Mark J. Luthra, Rajyalakshmi Medeiros, L. Jeffrey Wang, Sa A. Patel, Keyur P. Ok, Chi Young Cancer Med Clinical Cancer Research Adult T‐cell acute lymphoblastic leukemia (T‐ALL) is a heterogeneous group of acute leukemias that account for about one third of all cases of Philadelphia chromosome (Ph)‐negative ALL. Recently, a molecular classifier using the mutational status of NOTCH1, FBXW7, RAS, and PTEN (NFRP) has been shown to distinguish low‐ vs high‐risk groups in adult T‐ALL patients treated using the Berlin‐Frankfurt‐Münster ALL protocol. However, it is unknown if this molecular classifier can stratify adult T‐ALL patients treated with hyper‐CVAD ± nelarabine. We identified a relatively small cohort of 27 adults with T‐ALL who were uniformly treated with hyper‐CVAD ± nelarabine with available mutational analysis at time of diagnosis. The most commonly mutated genes in this group were NOTCH1 (52%), NRAS (22%), DNMT3A (19%), KRAS (15%), and TP53 (7%). The NFRP molecular classifier failed to stratify overall survival (OS; P = .84) and relapse‐free survival (RFS; P = .18) in this cohort. We developed a new stratification model combining K/NRAS and TP53 mutations as high‐risk factors and showed that mutations in these genes predicted poorer OS (P = .03) and RFS (P = .04). While the current study is limited by cohort size, these data suggest that the NFRP molecular classifier might not be applicable to adult T‐ALL patients treated with hyper‐CVAD ± nelarabine. RAS/TP53 mutation status, however, was useful in risk stratification in adults with T‐ALL. John Wiley and Sons Inc. 2019-12-05 /pmc/articles/PMC6997098/ /pubmed/31804006 http://dx.doi.org/10.1002/cam4.2757 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Sakhdari, Ali
Thakral, Beenu
Loghavi, Sanam
Kanagal‐Shamanna, Rashmi
Yin, C. Cameron
Zuo, Zhuang
Routbort, Mark J.
Luthra, Rajyalakshmi
Medeiros, L. Jeffrey
Wang, Sa A.
Patel, Keyur P.
Ok, Chi Young
RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD
title RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD
title_full RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD
title_fullStr RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD
title_full_unstemmed RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD
title_short RAS and TP53 can predict survival in adults with T‐cell lymphoblastic leukemia treated with hyper‐CVAD
title_sort ras and tp53 can predict survival in adults with t‐cell lymphoblastic leukemia treated with hyper‐cvad
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997098/
https://www.ncbi.nlm.nih.gov/pubmed/31804006
http://dx.doi.org/10.1002/cam4.2757
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