NFkB in multiple myeloma - L363 IKK inhibitor

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 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.