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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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Main Authors: Schümann, Franziska Lea (Author) , Groß, Elisabeth (Author) , Bauer, Marcus (Author) , Rohde, Christian (Author) , Sandmann, Sarah (Author) , Terziev, Denis (Author) , Müller, Lutz P. (Author) , Posern, Guido (Author) , Wienke, Andreas (Author) , Fend, Falko (Author) , Hansmann, Martin-Leo (Author) , Klapper, Wolfram (Author) , Rosenwald, Andreas (Author) , Stein, Harald (Author) , Dugas, Martin (Author) , Müller-Tidow, Carsten (Author) , Wickenhauser, Claudia (Author) , Binder, Mascha (Author) , Weber, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 5 December 2021
In: Biomedicines
Year: 2021, Volume: 9, Issue: 12, Pages: 1-16
ISSN:2227-9059
DOI:10.3390/biomedicines9121842
Online Access:Resolving-System, kostenfrei: https://doi.org/10.3390/biomedicines9121842
Resolving-System, kostenfrei: https://www.mdpi.com/2227-9059/9/12/1842
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Author Notes:Franziska Lea Schümann, Elisabeth Groß, Marcus Bauer, Christian Rohde, Sarah Sandmann, Denis Terziev, Lutz P. Müller, Guido Posern, Andreas Wienke, Falko Fend, Martin-Leo Hansmann, Wolfram Klapper, Andreas Rosenwald, Harald Stein, Martin Dugas, Carsten Müller-Tidow, Claudia Wickenhauser, Mascha Binder, Thomas Weber
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Summary: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.
Item Description:Gesehen am 21.07.2022
Physical Description:Online Resource
ISSN:2227-9059
DOI:10.3390/biomedicines9121842

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