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- W121133864 abstract "CD20 is a validated target for the immunotherapy of B lymphoid neoplasms, including ChronicLymphocytic Leukemia (CLL). We compared the activities of rituximab and GA101 (novel anti-CD20 antibody)on fresh human CLL cells in vitro. AnnexinV staining demonstrated induction of apoptosis after exposure torituximab or GA101. Unlike rituximab, GA101 induced a reduction of the mitochondrial transmembranepotential, an effect which could be partially inhibited by cyclosporin A and which was partially caspasedependent.GA101 was also found to induce the production of Reactive Oxygen Species. Analysis of pro- andanti-apoptotic protein content after exposure to antibodies demonstrated a strong degree of heterogeneity between samples. Bax underwent conformational activation and mitochondrial translocation upon exposure toantibodies in a caspase-independent manner. GA101 but not rituximab induced cleavage of caspase-8, -9 and -3.By transfecting CLL cells with anti-Bcl-xL siRNA using a sonoporation method, we found that reduction of BclxLcontent was associated with increased sensitivity to these antibodies. Our results suggest that apoptoticsignalization pathways differ between rituximab and GA101 with a greater involvement of the mitochondrialpathway for GA101. Inhibition of Bcl-xL could constitute an approach to sensitize CLL cells to the apoptoticeffects of anti-CD20 antibodies." @default.
- W121133864 created "2016-06-24" @default.
- W121133864 creator A5067770954 @default.
- W121133864 date "2010-12-23" @default.
- W121133864 modified "2023-09-24" @default.
- W121133864 title "Comparison of the cytotoxic mechanisms of anti-CD20 monoclonal antibodies Rituximab and GA101 in Chronic Lymphocytic Leukemia" @default.
- W121133864 hasPublicationYear "2010" @default.
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