RT Journal Article
A1 Bil, Jacek
A1 Winiarska, Magdalena
A1 Nowis, Dominika
A1 Bojarczuk, Kamil
A1 Dąbrowska-Iwanicka, Anna
A1 Basak, Grzegorz W.
A1 Sułek, Kazimierz
A1 Jakobisiak, Marek
A1 Golab, Jakub
T1 Bortezomib modulates surface CD20 in B-cell malignancies and affects rituximab-mediated complement-dependent cytotoxicity
JF Blood
JO Blood
YR 2010
DO 10.1182/blood-2009-09-244129
VO 115
IS 18
SP 3745
OP 3755
SN 0006-4971
AB Unresponsiveness to rituximab treatment develops in many patients prompting elucidation of underlying molecular pathways. It was recently observed that rituximab-resistant lymphoma cells exhibit up-regulation of components of the ubiquitin-proteasome system (UPS). Therefore, we investigated in more detail the role of this system in the regulation of CD20 levels and the influence of proteasome inhibitors on rituximab-mediated complement-dependent cytotoxicity (R-CDC). We observed that incubation of Raji cells with rituximab leads to increased levels of ubiquitinated CD20. However, inhibition of the UPS was not associated with up-regulation of surface CD20 levels, although it significantly increased its ubiquitination. Short-term (24 hours) incubation of Raji cells with 10 or 20nM bortezomib did not change surface CD20 levels, but sensitized CD20+ lymphoma cells to R-CDC. Prolonged (48 hours) incubation with 20nM bortezomib, or incubation with 50nM bortezomib for 24 hours led to a significant decrease in surface CD20 levels as well as R-CDC. These effects were partly reversed by bafilomycin A1, an inhibitor of lysosomal/autophagosomal pathway of protein degradation. These studies indicate that CD20 levels are regulated by 2 proteolytic systems and that the use of proteasome inhibitors may be associated with unexpected negative influence on R-CDC.
RD 11/15/2025
UL https://doi.org/10.1182/blood-2009-09-244129