Schrader, Alexandra, Meyer, Katharina, Walther, Neele, Stolz, Ailine, Feist, Maren, Hand, Elisabeth, von Bonin, Frederike, Evers, Maurits ORCID: 0000-0003-1252-7603, Kohler, Christian, Shirneshan, Katayoon, Vockerodt, Martina, Klapper, Wolfram, Szczepanowski, Monika, Murray, Paul G., Bastians, Holger, Truemper, Lorenz, Spang, Rainer ORCID: 0000-0002-1326-4297 and Kube, Dieter (2016). Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data. Oncotarget, 7 (30). S. 47061 - 47082. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through aIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR. 1, includes numerous cell cycle regulators. A reduced expression of BCR. 1 genes after BCR activation was observed in different cell lines and also in CD10(+) germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term aIgM treatment. Furthermore, an inverse correlation of BCR. 1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR. 1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schrader, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walther, NeeleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stolz, AilineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feist, MarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hand, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Bonin, FrederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evers, MauritsUNSPECIFIEDorcid.org/0000-0003-1252-7603UNSPECIFIED
Kohler, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shirneshan, KatayoonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vockerodt, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klapper, WolframUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szczepanowski, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murray, Paul G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bastians, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Truemper, LorenzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spang, RainerUNSPECIFIEDorcid.org/0000-0002-1326-4297UNSPECIFIED
Kube, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-269547
DOI: 10.18632/oncotarget.9219
Journal or Publication Title: Oncotarget
Volume: 7
Number: 30
Page Range: S. 47061 - 47082
Date: 2016
Publisher: IMPACT JOURNALS LLC
Place of Publication: ORCHARD PARK
ISSN: 1949-2553
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; DIFFERENTIAL EXPRESSION; PATHWAY ACTIVATION; MEDIATED APOPTOSIS; LYMPHOMA; TARGET; SIGNATURES; CD40; PROLIFERATION; PATHOGENESISMultiple languages
Oncology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26954

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