[PDF][PDF] Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma
CM Annunziata, RE Davis, Y Demchenko, W Bellamy… - Cancer cell, 2007 - cell.com
CM Annunziata, RE Davis, Y Demchenko, W Bellamy, A Gabrea, F Zhan, G Lenz…
Cancer cell, 2007•cell.comMechanisms of constitutive NF-κB signaling in multiple myeloma are unknown. An inhibitor
of IκB kinase β (IKKβ) targeting the classical NF-κB 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-κB pathways. A majority of primary
myeloma patient samples and cell lines had elevated NF-κB target gene expression, often …
of IκB kinase β (IKKβ) targeting the classical NF-κB 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-κB pathways. A majority of primary
myeloma patient samples and cell lines had elevated NF-κB target gene expression, often …
Summary
Mechanisms of constitutive NF-κB signaling in multiple myeloma are unknown. An inhibitor of IκB kinase β (IKKβ) targeting the classical NF-κB 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-κB pathways. A majority of primary myeloma patient samples and cell lines had elevated NF-κB 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-κB pathway is frequent in myeloma and suggest that IKKβ inhibitors hold promise for the treatment of this disease.
cell.com