ELEVATED BCL-2 BAX ARE A CONSISTENT FEATURE OF APOPTOSIS RESISTANCE IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA AND ARE CORRELATED WITH IN-VIVO CHEMORESISTANCE/

We investigated the relationship between drug resistance and Bcl-2/Bax in B-cell chronic lymphocytic leukaemia (B-CLL). Apoptosis was induce d in vitro with chlorambucil and cell death was monitored by dual-labe lled FAGS analysis using Annexin V and propidium iodide, Bcl-2 and Bar protein expression was quantified using FAGS and a correlation betwee n drug-induced apoptosis and Bcl-2/Bax was established, Cells were the n sorted into viable and non-viable populations according to their for ward and side-scatter characteristics and re-analysed for Bcl-2/Bax. T he most resistant cells had elevated Bcl-2 levels and low Bar expressi on, Furthermore, those cells which were undergoing apoptosis showed on ly a marginal reduction in Bcl-2 expression, but significantly elevate d Bar expression following exposure to chlorambucil. The Bcl-2/Bax was significantly greater in the cell fractions resistant to chlorambucil -induced apoptosis. This observation further supports the suggestion t hat Bar is the pivotal protein in determining the fate of cells follow ing apoptotic signals.