Cargando…

c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study

Relationships between c-Rel and GCB-DLBCLs remain unclear. We found that strong c-Rel DNA-binding activity was mostly found in GCBs on two independent series of 48 DLBCLs and 66 DLBCLs, the latter issued from the GHEDI series. c-Rel DNA-binding activity was associated with increased REL mRNA express...

Descripción completa

Detalles Bibliográficos
Autores principales: Faumont, Nathalie, Taoui, Oussama, Collares, Davi, Jais, Jean-Philippe, Leroy, Karen, Prévaud, Léa, Jardin, Fabrice, Molina, Thierry J., Copie-Bergman, Christiane, Petit, Barbara, Gourin, Marie-Pierre, Bordessoule, Dominique, Troutaud, Danielle, Baud, Véronique, Feuillard, Jean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095348/
https://www.ncbi.nlm.nih.gov/pubmed/33959502
http://dx.doi.org/10.3389/fonc.2021.638897
_version_ 1783688061608001536
author Faumont, Nathalie
Taoui, Oussama
Collares, Davi
Jais, Jean-Philippe
Leroy, Karen
Prévaud, Léa
Jardin, Fabrice
Molina, Thierry J.
Copie-Bergman, Christiane
Petit, Barbara
Gourin, Marie-Pierre
Bordessoule, Dominique
Troutaud, Danielle
Baud, Véronique
Feuillard, Jean
author_facet Faumont, Nathalie
Taoui, Oussama
Collares, Davi
Jais, Jean-Philippe
Leroy, Karen
Prévaud, Léa
Jardin, Fabrice
Molina, Thierry J.
Copie-Bergman, Christiane
Petit, Barbara
Gourin, Marie-Pierre
Bordessoule, Dominique
Troutaud, Danielle
Baud, Véronique
Feuillard, Jean
author_sort Faumont, Nathalie
collection PubMed
description Relationships between c-Rel and GCB-DLBCLs remain unclear. We found that strong c-Rel DNA-binding activity was mostly found in GCBs on two independent series of 48 DLBCLs and 66 DLBCLs, the latter issued from the GHEDI series. c-Rel DNA-binding activity was associated with increased REL mRNA expression. Extending the study to the whole GHEDI and Lenz DLBCL published series of 202 and 233 cases, it was found that the c-Rel gene expression profile (GEP) overlapped partially (12%) but only with the GCB GEP and not with the GEP of ABC-DLBCLs. Cases with both overexpression of REL mRNA and c-Rel GEP were defined as those having a c-Rel signature. These cases were GCBs in 88 and 83% of the GHEDI or Lenz’s DLBCL series respectively. The c-Rel signature was also associated with various recurrent GCB-DLBCL genetic events, including REL gains, BCL2 translocation, MEF2B, EZH2, CREBBP, and TNFRSF14 mutations and with the EZB GCB genetic subtype. By CGH array, the c-Rel signature was specifically correlated with 2p15-16.1 amplification that includes XPO1, BCL11A, and USP34 and with the 22q11.22 deletion that covers IGLL5 and PRAME. The total number of gene copy number aberrations, so-called genomic imbalance complexity, was decreased in cases with the c-Rel signature. These cases exhibited a better overall survival. Functionally, overexpression of c-Rel induced its constitutive nuclear localization and protected cells against apoptosis while its repression tended to increase cell death. These results show that, clinically and biologically, c-Rel is the pivotal NF-κB subunit in the GCB-DLBCL subgroup. Functionally, c-Rel overexpression could directly promote DLBCL tumorigenesis without need for further activation signals.
format Online
Article
Text
id pubmed-8095348
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-80953482021-05-05 c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study Faumont, Nathalie Taoui, Oussama Collares, Davi Jais, Jean-Philippe Leroy, Karen Prévaud, Léa Jardin, Fabrice Molina, Thierry J. Copie-Bergman, Christiane Petit, Barbara Gourin, Marie-Pierre Bordessoule, Dominique Troutaud, Danielle Baud, Véronique Feuillard, Jean Front Oncol Oncology Relationships between c-Rel and GCB-DLBCLs remain unclear. We found that strong c-Rel DNA-binding activity was mostly found in GCBs on two independent series of 48 DLBCLs and 66 DLBCLs, the latter issued from the GHEDI series. c-Rel DNA-binding activity was associated with increased REL mRNA expression. Extending the study to the whole GHEDI and Lenz DLBCL published series of 202 and 233 cases, it was found that the c-Rel gene expression profile (GEP) overlapped partially (12%) but only with the GCB GEP and not with the GEP of ABC-DLBCLs. Cases with both overexpression of REL mRNA and c-Rel GEP were defined as those having a c-Rel signature. These cases were GCBs in 88 and 83% of the GHEDI or Lenz’s DLBCL series respectively. The c-Rel signature was also associated with various recurrent GCB-DLBCL genetic events, including REL gains, BCL2 translocation, MEF2B, EZH2, CREBBP, and TNFRSF14 mutations and with the EZB GCB genetic subtype. By CGH array, the c-Rel signature was specifically correlated with 2p15-16.1 amplification that includes XPO1, BCL11A, and USP34 and with the 22q11.22 deletion that covers IGLL5 and PRAME. The total number of gene copy number aberrations, so-called genomic imbalance complexity, was decreased in cases with the c-Rel signature. These cases exhibited a better overall survival. Functionally, overexpression of c-Rel induced its constitutive nuclear localization and protected cells against apoptosis while its repression tended to increase cell death. These results show that, clinically and biologically, c-Rel is the pivotal NF-κB subunit in the GCB-DLBCL subgroup. Functionally, c-Rel overexpression could directly promote DLBCL tumorigenesis without need for further activation signals. Frontiers Media S.A. 2021-04-20 /pmc/articles/PMC8095348/ /pubmed/33959502 http://dx.doi.org/10.3389/fonc.2021.638897 Text en Copyright © 2021 Faumont, Taoui, Collares, Jais, Leroy, Prévaud, Jardin, Molina, Copie-Bergman, Petit, Gourin, Bordessoule, Troutaud, Baud and Feuillard https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Faumont, Nathalie
Taoui, Oussama
Collares, Davi
Jais, Jean-Philippe
Leroy, Karen
Prévaud, Léa
Jardin, Fabrice
Molina, Thierry J.
Copie-Bergman, Christiane
Petit, Barbara
Gourin, Marie-Pierre
Bordessoule, Dominique
Troutaud, Danielle
Baud, Véronique
Feuillard, Jean
c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study
title c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study
title_full c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study
title_fullStr c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study
title_full_unstemmed c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study
title_short c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study
title_sort c-rel is the pivotal nf-κb subunit in germinal center diffuse large b-cell lymphoma: a lysa study
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095348/
https://www.ncbi.nlm.nih.gov/pubmed/33959502
http://dx.doi.org/10.3389/fonc.2021.638897
work_keys_str_mv AT faumontnathalie crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT taouioussama crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT collaresdavi crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT jaisjeanphilippe crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT leroykaren crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT prevaudlea crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT jardinfabrice crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT molinathierryj crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT copiebergmanchristiane crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT petitbarbara crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT gourinmariepierre crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT bordessouledominique crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT troutauddanielle crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT baudveronique crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy
AT feuillardjean crelisthepivotalnfkbsubunitingerminalcenterdiffuselargebcelllymphomaalysastudy