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
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ABSTRACT:
INSTRUMENT(S): [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
SUBMITTER: 
Christian W Kohler
PROVIDER: GSE71725 | GEO | 2016-06-07
SECONDARY ACCESSION(S): GSE71721 GSE68761PRJNA291920 GSE71724
REPOSITORIES: GEO
Dataset's files
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Publications
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.
Schrader Alexandra A Meyer Katharina K Walther Neele N Stolz Ailine A Feist Maren M Hand Elisabeth E von Bonin Frederike F Evers Maurits M Kohler Christian C Shirneshan Katayoon K Vockerodt Martina M Klapper Wolfram W Szczepanowski Monika M Murray Paul G PG Bastians Holger H Trümper Lorenz L Spang Rainer R Kube Dieter D
Oncotarget 20160701 30
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 αIgM 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 wa ...[more]
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Project description:To discover new essential regulatory pathways in B lymphoma cells a combined analysis of experimental and clinical high throughput data was performed. Among others, a specific cluster of coherently expressed genes named BCR.1 was identified in primary lymphoma samples. These coherently expressed genes are suppressed by α-IgM treatement of lymphoma cells in vitro. This B cell receptor activation leads to a G2 phase prolongation, delayed entry into the M phase, an overall diminished capacity of the cells to enter into mitosis and defects in metaphases. Cytogenetic changes are detected under long term α-IgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc coregulated genes in distinct groups of lymphoma patients is observed. In addition to the impact of c-Myc in the regulation of cell cycle regulators, BCR.1 genes are regulated by a combined action of IKK2, MAPK14 and JNK. Finally, the BCR.1 index discriminates activated B cell like and germinal centre B cell like diffuse large B cell lymphoma. Therefore, a new regulatory circuit is described affecting cell cycle and chromosome instability in B cells. Overall design: 20 CD10+ B cell samples were hybridized to HGU133+2 Affymetrix GeneChips.
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