Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma.
Journal Article (Journal Article)
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 lines had elevated NF-kappaB target gene expression, often associated with genetic or epigenetic alteration of NIK, TRAF3, CYLD, BIRC2/BIRC3, CD40, NFKB1, or NFKB2. These data demonstrate that addiction to the NF-kappaB pathway is frequent in myeloma and suggest that IKKbeta inhibitors hold promise for the treatment of this disease.
Full Text
Duke Authors
Cited Authors
- Annunziata, CM; Davis, RE; Demchenko, Y; Bellamy, W; Gabrea, A; Zhan, F; Lenz, G; Hanamura, I; Wright, G; Xiao, W; Dave, S; Hurt, EM; Tan, B; Zhao, H; Stephens, O; Santra, M; Williams, DR; Dang, L; Barlogie, B; Shaughnessy, JD; Kuehl, WM; Staudt, LM
Published Date
- August 2007
Published In
Volume / Issue
- 12 / 2
Start / End Page
- 115 - 130
PubMed ID
- 17692804
Pubmed Central ID
- PMC2730509
International Standard Serial Number (ISSN)
- 1535-6108
Digital Object Identifier (DOI)
- 10.1016/j.ccr.2007.07.004
Language
- eng
Conference Location
- United States