Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Schrader, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Walther, Neele UNSPECIFIED UNSPECIFIED UNSPECIFIED Stolz, Ailine UNSPECIFIED UNSPECIFIED UNSPECIFIED Feist, Maren UNSPECIFIED UNSPECIFIED UNSPECIFIED Hand, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED von Bonin, Frederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Evers, Maurits UNSPECIFIED orcid.org/0000-0003-1252-7603 UNSPECIFIED Kohler, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Shirneshan, Katayoon UNSPECIFIED UNSPECIFIED UNSPECIFIED Vockerodt, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Klapper, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Szczepanowski, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Murray, Paul G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bastians, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Truemper, Lorenz UNSPECIFIED UNSPECIFIED UNSPECIFIED Spang, Rainer UNSPECIFIED orcid.org/0000-0002-1326-4297 UNSPECIFIED Kube, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language NF-KAPPA-B; DIFFERENTIAL EXPRESSION; PATHWAY ACTIVATION; MEDIATED APOPTOSIS; LYMPHOMA; TARGET; SIGNATURES; CD40; PROLIFERATION; PATHOGENESIS Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26954