Transcriptomics,Genomics

Dataset Information

39

NFkB in multiple myeloma - L363 IKK inhibitor


ABSTRACT: Mechanisms of constitutive NF-kappaB signaling in multiple myeloma are unknown. An inhibitor of IkappaB kinase beta (IKKbeta), targeting the classical NF-kappaB pathway, was lethal to many myeloma cell lines. Several had elevated expression of NIK due to genomic alterations or enhanced protein stability while others had inactivating mutations or deletion of TRAF3. Both abnormalities triggered the classical and alternative NF-kappaB pathways. A majority of primary myeloma patient samples and cell lines had elevated NF-kappaB target gene expression, often associated with genetic and epigenetic alteration of NIK, TRAF3, CYLD, BIRC2/BIRC3, CD40, NFKB1, and NFKB2. These genetic and functional data demonstrate that addiction to the NF-kappaB pathway is a frequent feature of myeloma and suggest that IKKbeta inhibitors hold promise for the treatment of this disease. Keywords: time series design Overall design: L363 cells were treated with IKKb inhibitor MLN120b for 8h, 12h, 24h. Three timecourses, a total of 8 samples, were analyzed in comparison to cells treated with DMSO (solvent) alone.

INSTRUMENT(S): NCI/Staudt human 15K v13

SUBMITTER: Christina Annunziata  

PROVIDER: GSE8476 | GEO | 2007-10-29

SECONDARY ACCESSION(S): PRJNA105361

REPOSITORIES: GEO

altmetric image

Publications


Mechanisms of constitutive NF-kappaB signaling in multiple myeloma are unknown. An inhibitor of IkappaB kinase beta (IKKbeta) targeting the classical NF-kappaB pathway was lethal to many myeloma cell lines. Several cell lines had elevated expression of NIK due to genomic alterations or protein stabilization, while others had inactivating mutations of TRAF3; both kinds of abnormality triggered the classical and alternative NF-kappaB pathways. A majority of primary myeloma patient samples and cell  ...[more]

Similar Datasets

2007-10-29 | GSE8477 | GEO
2009-09-11 | GSE18047 | GEO
| GSE31272 | GEO
2015-06-18 | E-GEOD-68317 | ArrayExpress
| GSE88949 | GEO
2010-01-20 | GSE19841 | GEO
2010-06-19 | E-GEOD-19841 | ArrayExpress
2009-03-24 | GSE15264 | GEO
| GSE94610 | GEO
2013-12-01 | E-GEOD-52435 | ArrayExpress