Author/Authors :
Annunziata، نويسنده , , Christina M. and Davis، نويسنده , , R. Eric and Demchenko، نويسنده , , Yulia and Bellamy، نويسنده , , William and Gabrea، نويسنده , , Ana and Zhan، نويسنده , , Fenghuang and Lenz، نويسنده , , Georg and Hanamura، نويسنده , , Ichiro and Wright، نويسنده , , George and Xiao، نويسنده , , Wenming and Dave، نويسنده , , Sandeep and Hurt، نويسنده , , Elaine M. and Tan، نويسنده , , Bruce and Zhao، نويسنده , , Hong and Stephens، نويسنده , , Owen and Santra، نويسنده , , Madhumita and Williams، نويسنده , , David R. and Dang، نويسنده , , Lenny and Barlogie، نويسنده , , Bart and Shaughnessy Jr.، نويسنده , , John D. and Kuehl، نويسنده , , W. Michael and Staudt، نويسنده , , Louis M.، نويسنده ,
Abstract :
Summary
isms 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.
