Hairy-cell leukaemia as a model for drug development.

Hairy-cell leukaemia cells have a low rate of growth but an even lower rate of apoptosis. Accordingly, this malignancy is an excellent model for studying the effects of drugs on the pathways of apoptosis independently of cell proliferation. The remarkable effectiveness of 2-chlorodeoxyadenosine in hairy-cell leukaemia affirms the feasibility of developing drugs that can destroy even non-proliferating malignant cells. The major nucleotide metabolite of 2-chlorodeoxyadenosine accumulates selectively in lymphocytes and co-activates two key apoptosis-regulating enzymes: poly(ADP-ribose) polymerase and Apaf-1/caspase-9. The ability of 2-chlorodeoxyadenosine to induce durable remissions in hairy-cell leukaemia may also be attributable to its effects on lymphocytes and monocytes in the microenvironment, although this latter effect remains to be proven experimentally.