Several reports demonstrated that the activation of Nuclear Factor-kappa B NF-κB is essential for the pathogenesis of multiple myeloma (MM). We analyzed the nuclear localization of NF-κB 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-κB 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-κB. In mesenchymal cells from MM-patients NF-κB was clearly present in the nucleus. In addition, the proteasome inhibitor Bortezomib, which is described to antagonize NF-κB activity, had a consistent antitumor activity against both chemoresistant and chemosensitive MM-cells, regardless the NF-κB localization, thus suggesting the existence of other molecular targets of proteasome inhibitors in MM. © 2010 Elsevier Ltd.
Conticello, C., Giuffrida, R., Adamo, L., Anastasi, G., Martinetti, D., Salomone, E., Colarossi, C., Amato, G., Gorgone, A., Romano, A., Iannolo, G., De Maria Marchiano, R., Giustolisi, R., Gulisano, M., Di Raimondo, F., NF-KB localization in multiple myeloma plasma cells and mesenchymal cells, <<LEUKEMIA RESEARCH>>, 2011; 35 (1): 52-60. [doi:10.1016/j.leukres.2010.06.023] [http://hdl.handle.net/10807/112482]
NF-KB localization in multiple myeloma plasma cells and mesenchymal cells
De Maria Marchiano, Ruggero;
2011
Abstract
Several reports demonstrated that the activation of Nuclear Factor-kappa B NF-κB is essential for the pathogenesis of multiple myeloma (MM). We analyzed the nuclear localization of NF-κB 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-κB 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-κB. In mesenchymal cells from MM-patients NF-κB was clearly present in the nucleus. In addition, the proteasome inhibitor Bortezomib, which is described to antagonize NF-κB activity, had a consistent antitumor activity against both chemoresistant and chemosensitive MM-cells, regardless the NF-κB localization, thus suggesting the existence of other molecular targets of proteasome inhibitors in MM. © 2010 Elsevier Ltd.
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