NF-κB localization in multiple myeloma plasma cells and mesenchymal cells

Several reports demonstrated that the activation of Nuclear Factor-kappa B NF-kappa B is essential for the pathogenesis of multiple myeloma (MM). We analyzed the nuclear localization of NF-kappa B in MM-cells derived from 60 different patients with MM at presentation and in relapse, as well as in three myeloma cell lines. Nuclear localization (the active form) of NF-kappa B was detected in only one MM-sample from a refractory patient and in two samples from relapsed patients, while all the other samples, including the MM-cell lines, almost exclusively express the cytoplasmic (inactive) form of NF-kappa B. In mesenchymal cells from MM-patients NF-kappa B was clearly present in the nucleus. In addition, the proteasome inhibitor Bortezomib, which is described to antagonize NF-kappa B activity, had a consistent antitumor activity against both chemoresistant and chemosensitive MM-cells, regardless the NF-kappa B localization, thus suggesting the existence of other molecular targets of proteasome inhibitors in MM. (C) 2010 Elsevier Ltd. All rights reserved.