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The Unsolved Puzzle of c-Rel in B Cell Lymphoma

Institute of Experimental Hematology, School of Medicine, Technical University Munich, Ismaninger Straße 22, 81675 Munich, Germany
German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Authors to whom correspondence should be addressed.
Current address: Merck KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany.
Cancers 2019, 11(7), 941;
Received: 23 May 2019 / Revised: 28 June 2019 / Accepted: 29 June 2019 / Published: 4 July 2019
(This article belongs to the Special Issue NF-kappaB signalling pathway)
PDF [879 KB, uploaded 4 July 2019]


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. View Full-Text
Keywords: c-Rel; NF-κB; B cells; REL gene locus amplification; lymphoma; FL; DLBCL; PMBCL; cHL c-Rel; NF-κB; B cells; REL gene locus amplification; lymphoma; FL; DLBCL; PMBCL; cHL

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Kober-Hasslacher, M.; Schmidt-Supprian, M. The Unsolved Puzzle of c-Rel in B Cell Lymphoma. Cancers 2019, 11, 941.

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