Unknown,Transcriptomics,Genomics,Proteomics

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Expression of ZAP-70 in CLL activates NF-M-NM-:B signaling


ABSTRACT: 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-M-NM-:B target genes interleukin-1M-NM-2 (IL-1M-NM-2), IL-6 and IL-8 upon BCR triggering. This could be blocked by inhibition of NF-M-NM-:B signaling through inhibition of IM-NM-:B kinases (IKK). Transcriptome analysis identified a NF-M-NM-:B RelA signature imposed by ZAP-70 expression in BCR stimulated CLL cells. We conclude that ZAP-70 acts directly as an amplifier of NF-M-NM-:B 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)

ORGANISM(S): Homo sapiens

SUBMITTER: Valerie Pede 

PROVIDER: E-GEOD-51286 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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