E-GEOD-51286 - Expression of ZAP-70 in CLL activates NF-κB signaling

Status
Released on 22 October 2013, last updated on 3 June 2014
Organism
Homo sapiens
Samples (22)
Array (1)
Protocols (7)
Description
Chronic lymphocytic leukemia (CLL) is a disease with a highly variable prognosis. The clinical course can however be predicted thanks to prognostic markers. Poor prognosis is associated with expression of a B cell receptor (BCR) from unmutated immunoglobulin variable heavy-chain genes (IgVH) and expression of zeta associated protein of 70 kDa (ZAP-70). The reason why ZAP-70 expression is associated with poor prognosis and whether the protein has a direct pathogenic function is at present unknown. By transfer of ZAP-70 to CLL cells, we show here that expression of ZAP-70 in CLL cells leads to increased expression of the NF-κB target genes interleukin-1β (IL-1β), IL-6 and IL-8 upon BCR triggering. This could be blocked by inhibition of NF-κB signaling through inhibition of IκB kinases (IKK). Transcriptome analysis identified a NF-κB RelA signature imposed by ZAP-70 expression in BCR stimulated CLL cells. We conclude that ZAP-70 acts directly as an amplifier of NF-κB signaling in CLL cells which could be an underlying mechanism for its association with poor prognosis and which may represent a therapeutic target. 22 patient samples, Stimulated for 3h or 24h, Electroporated with capped ZAP-70 mRNA or uncapped ZAP-70 mRNA (negative control)
Experiment type
transcription profiling by array 
Contacts
Bruno Verhasselt, Evelien Naessens, Hanne Vanderstraeten, Jan Philippé, Rombout Ans, Valerie Pede, Vermeire Jolien
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-51286.idf.txt
Sample and data relationshipE-GEOD-51286.sdrf.txt
Processed data (1)E-GEOD-51286.processed.1.zip
Array designA-MEXP-1171.adf.txt
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