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.