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Thursday 01 April 2004

Sensitivity of B-cell chronic lymphocytic leukemia to Rituximab and Campath-1H and correlation with the expression of cell cycle regulatory proteins.

By: Grdisa M.

Croat Med J 2004 Apr;45(2):136-41

AIM: To assess the effect of monoclonal antibodies anti-CD20 (Rituximab) and anti-CD52 (Campath-1H) on the viability of B cells from patients with B cell chronic lymphocytic leukemia (B-CLL) in comparison with a cytotoxic drug fludarabine (Fluda), and to determine the influence of these agents on the expression of cell cycle regulatory proteins in vitro. METHODS: B-CLL cells were incubated in vitro in the presence of Rituximab, Campath-1H, and Fluda. The viability of the cells was measured by MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-dyphenyltetrazolium bromide). Gel electrophoresis and Western blotting were used to determine the effect of these agents on the expression of cell cycle regulatory proteins in vitro. RESULTS: Both monoclonal antibodies, Rituximab and Campath-1H, were less toxic than Fluda to B-CLL cells. Combination of Campath-1H or Rituximab with Fluda did not have a stronger effect on the cells than Fluda alone. Both antibodies decreased the expression of p27 protein and increased the expression of p23; Fluda had a similar effect. The extent of cyclin D3 and cyclin E expression did not change significantly. The expression of cyclin D2 was slightly increased in the presence of Campath-1H, but in the presence of Rituximab it either decreased slightly or remained the same. Treatment of B-CLL cells with Fluda alone induced significant decrease in cyclin D2 expression. CONCLUSION: These results demonstrated that monoclonal antibodies Campath-1H and Rituximab antibodies, as well as a cytotoxic drug fludarabine, had cytotoxic effects on B-CLL cells. They most likely induce apoptosis of B-CLL cells, but their activity is mediated through different pathways.

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