Naslov
Induction of apoptosis in B-CLL cells by different signal transduction pathway

Autori
Grdiša, Mira

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
EHA'02 / - Firenza : München, 2002

Skup
7th Congres of the European Haematology Association

Mjesto i datum
Firenca, Italija, 05.06.2002. - 10.06.2002

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
B-CLL; CD40L; Rituximab; Campath 1H; cell cycle

Sažetak
Immunological treatment of tumors opened a new therapeutic aproaches in the patients resistant to chemotherapy. In this work we examined the influence of monoclonal antibodies (Campath-1H, Rituximab) and interaction through CD40/CD40L on viability of B-cells from CLL patients. The effect of these agents, wich probably act through different mechanisms, on the expression of cell cycle regulatory proteins “ in vitro” was examined. Campath-1H is a human IgG1 anti CD52 monoclonal antibody. It’ s expressed on all B- and T- cells. Rituximab is a chimeric monoclonal antibody directed against CD20 receptor, expressed on all B-cells. Treatment of B-CLL with monoclonal antibodies (Rituximab and Campath-1H) was variable among the patients. To induce cytotoxic cell death, both Ab’ s required the presence of crosslink-antibody. In comparison with Fluda, they exerted a lower cytotoxic effect. In 5 of 9 patients a cytotoxic effect of Campath-1H and Rituximab was similar and in 4 patients the effect of campath-1H was better. After treatment with Ab’ s, a level of p27 decreased and p23 increased. Similar effect was seen after treatment with Fluda. The levels of cyc D3 and E didn’ t change. A level of cyc D2 didn’ t change in the presence of Rituximab, and little increased in the presence of Campath-1H. Fluda induced remarcable decreased of cyc D2. All agents (Rituximab, Campath-1H, Fluda) induced apoptosis in B-CLL cells but probably with a different mechanism of action. CD40 ligand (CD40L, CD154) is released from mature T-cells and specificly binds on CD40 receptor, expressed on B-cells. CD40/CD40L interaction influences on different signal transduction pathways: on immunological reactions, maturation of T-lymphocytes, growth and differentiation of B-cells, maturation of dendritic cells etc. Defective expression of CD40L can results in severe immunodeficiency. Treatment of B-CLL in vitro with CD40L resulted in better survival of the cells, similar as with IL-4. It posponed but it didn’ t prevent a cytotoxic effect of Fluda. CD40L in combination with IL-4 acts synergistic. These two pathways induced increasing expression of cyc D2, D3 and E, phosphorylation of pRb and decreasing of p27. By FACS analysis some progression of cell cycle was noticed.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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