Bcl-2 antisense oligonucleotides enhance the cytotoxicity of Chlorambucil in B-cell chronic lymphocytic leukaemia cells

We have previously shown that the Bcl-2 antisense oligonucleotide ODN 2009 can induce apoptosis in B-cell chronic lymphocytic leukaemia (B-CLL) cells. In this study we evaluated whether ODN 2009 could increase the sensitivity of B-CLL cells to Chlorambucil-induced cell death in vitro in order to est ablish whether the notion of antisense-mediated chemosensitisation could be applied to B-CLL. Bcl-2 antisense in combination with Chlorambucil resulte d in a more marked reduction in Bcl-2 protein expression (p = 0.003), enhan ced Bax expression (p < 0.0001) and increased apoptosis when compared to ce lls incubated with Chlorambucil alone (p = 0.03). This increased in vitro c ytotoxicity demonstrates a proof of the concept that a combination of Bcl-2 antisense oligonucleotides with conventional chemotherapeutic drugs may el icit an enhanced therapeutic effect in B-CLL and should therefore be consid ered for further investigation in the form of a clinical trial.