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The Unsolved Puzzle of c-Rel in B Cell Lymphoma

Aberrant constitutive activation of Rel/NF-κB transcription factors is a hallmark of numerous cancers. Of the five Rel family members, c-Rel has the strongest direct links to tumorigenesis. c-Rel is the only member that can malignantly transform lymphoid cells in vitro. Furthermore, c-Rel is implica...

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Detalles Bibliográficos
Autores principales: Kober-Hasslacher, Maike, Schmidt-Supprian, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678315/
https://www.ncbi.nlm.nih.gov/pubmed/31277480
http://dx.doi.org/10.3390/cancers11070941
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author Kober-Hasslacher, Maike
Schmidt-Supprian, Marc
author_facet Kober-Hasslacher, Maike
Schmidt-Supprian, Marc
author_sort Kober-Hasslacher, Maike
collection PubMed
description Aberrant constitutive activation of Rel/NF-κB transcription factors is a hallmark of numerous cancers. Of the five Rel family members, c-Rel has the strongest direct links to tumorigenesis. c-Rel is the only member that can malignantly transform lymphoid cells in vitro. Furthermore, c-Rel is implicated in human B cell lymphoma through the frequent occurrence of REL gene locus gains and amplifications. In normal physiology, high c-Rel expression predominates in the hematopoietic lineage and a diverse range of stimuli can trigger enhanced expression and activation of c-Rel. Both expression and activation of c-Rel are tightly regulated on multiple levels, indicating the necessity to keep its functions under control. In this review we meta-analyze and integrate studies reporting gene locus aberrations to provide an overview on the frequency of REL gains in human B cell lymphoma subtypes, namely follicular lymphoma, diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, and classical Hodgkin lymphoma. We also summarize current knowledge on c-Rel expression and protein localization in these human B cell lymphomas and discuss the co-amplification of BCL11A with REL. In addition, we highlight and illustrate key pathways of c-Rel activation and regulation with a specific focus on B cell biology.
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spelling pubmed-66783152019-08-19 The Unsolved Puzzle of c-Rel in B Cell Lymphoma Kober-Hasslacher, Maike Schmidt-Supprian, Marc Cancers (Basel) Review Aberrant constitutive activation of Rel/NF-κB transcription factors is a hallmark of numerous cancers. Of the five Rel family members, c-Rel has the strongest direct links to tumorigenesis. c-Rel is the only member that can malignantly transform lymphoid cells in vitro. Furthermore, c-Rel is implicated in human B cell lymphoma through the frequent occurrence of REL gene locus gains and amplifications. In normal physiology, high c-Rel expression predominates in the hematopoietic lineage and a diverse range of stimuli can trigger enhanced expression and activation of c-Rel. Both expression and activation of c-Rel are tightly regulated on multiple levels, indicating the necessity to keep its functions under control. In this review we meta-analyze and integrate studies reporting gene locus aberrations to provide an overview on the frequency of REL gains in human B cell lymphoma subtypes, namely follicular lymphoma, diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, and classical Hodgkin lymphoma. We also summarize current knowledge on c-Rel expression and protein localization in these human B cell lymphomas and discuss the co-amplification of BCL11A with REL. In addition, we highlight and illustrate key pathways of c-Rel activation and regulation with a specific focus on B cell biology. MDPI 2019-07-04 /pmc/articles/PMC6678315/ /pubmed/31277480 http://dx.doi.org/10.3390/cancers11070941 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kober-Hasslacher, Maike
Schmidt-Supprian, Marc
The Unsolved Puzzle of c-Rel in B Cell Lymphoma
title The Unsolved Puzzle of c-Rel in B Cell Lymphoma
title_full The Unsolved Puzzle of c-Rel in B Cell Lymphoma
title_fullStr The Unsolved Puzzle of c-Rel in B Cell Lymphoma
title_full_unstemmed The Unsolved Puzzle of c-Rel in B Cell Lymphoma
title_short The Unsolved Puzzle of c-Rel in B Cell Lymphoma
title_sort unsolved puzzle of c-rel in b cell lymphoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678315/
https://www.ncbi.nlm.nih.gov/pubmed/31277480
http://dx.doi.org/10.3390/cancers11070941
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