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Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas

T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecula...

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Autores principales: Schümann, Franziska Lea, Groß, Elisabeth, Bauer, Marcus, Rohde, Christian, Sandmann, Sarah, Terziev, Denis, Müller, Lutz P., Posern, Guido, Wienke, Andreas, Fend, Falko, Hansmann, Martin-Leo, Klapper, Wolfram, Rosenwald, Andreas, Stein, Harald, Dugas, Martin, Müller-Tidow, Carsten, Wickenhauser, Claudia, Binder, Mascha, Weber, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698684/
https://www.ncbi.nlm.nih.gov/pubmed/34944658
http://dx.doi.org/10.3390/biomedicines9121842
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author Schümann, Franziska Lea
Groß, Elisabeth
Bauer, Marcus
Rohde, Christian
Sandmann, Sarah
Terziev, Denis
Müller, Lutz P.
Posern, Guido
Wienke, Andreas
Fend, Falko
Hansmann, Martin-Leo
Klapper, Wolfram
Rosenwald, Andreas
Stein, Harald
Dugas, Martin
Müller-Tidow, Carsten
Wickenhauser, Claudia
Binder, Mascha
Weber, Thomas
author_facet Schümann, Franziska Lea
Groß, Elisabeth
Bauer, Marcus
Rohde, Christian
Sandmann, Sarah
Terziev, Denis
Müller, Lutz P.
Posern, Guido
Wienke, Andreas
Fend, Falko
Hansmann, Martin-Leo
Klapper, Wolfram
Rosenwald, Andreas
Stein, Harald
Dugas, Martin
Müller-Tidow, Carsten
Wickenhauser, Claudia
Binder, Mascha
Weber, Thomas
author_sort Schümann, Franziska Lea
collection PubMed
description T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients.
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spelling pubmed-86986842021-12-24 Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas Schümann, Franziska Lea Groß, Elisabeth Bauer, Marcus Rohde, Christian Sandmann, Sarah Terziev, Denis Müller, Lutz P. Posern, Guido Wienke, Andreas Fend, Falko Hansmann, Martin-Leo Klapper, Wolfram Rosenwald, Andreas Stein, Harald Dugas, Martin Müller-Tidow, Carsten Wickenhauser, Claudia Binder, Mascha Weber, Thomas Biomedicines Article T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients. MDPI 2021-12-05 /pmc/articles/PMC8698684/ /pubmed/34944658 http://dx.doi.org/10.3390/biomedicines9121842 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schümann, Franziska Lea
Groß, Elisabeth
Bauer, Marcus
Rohde, Christian
Sandmann, Sarah
Terziev, Denis
Müller, Lutz P.
Posern, Guido
Wienke, Andreas
Fend, Falko
Hansmann, Martin-Leo
Klapper, Wolfram
Rosenwald, Andreas
Stein, Harald
Dugas, Martin
Müller-Tidow, Carsten
Wickenhauser, Claudia
Binder, Mascha
Weber, Thomas
Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
title Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
title_full Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
title_fullStr Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
title_full_unstemmed Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
title_short Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
title_sort divergent effects of ezh1 and ezh2 protein expression on the prognosis of patients with t-cell lymphomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698684/
https://www.ncbi.nlm.nih.gov/pubmed/34944658
http://dx.doi.org/10.3390/biomedicines9121842
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