Mechanisms of action.

There are 3 modes of action of the adenine deoxynucleoside analogs in nonproliferating CLL cells. In the cells the drugs are transformed into their triphosphate form, which induce DNA damage, mitochondrial dysfunction, and binding to APAF-1 and activation of the caspase pathway. F-ara-A kills cells mainly by DNA damage and Apaf-1 activation. 2CdA and CaFdA also interfere with mitochondrial function. The different effects of the adenine deoxynucleosides in various lymphoid malignancies may reflect the relative importance of the 3 mechanisms in apoptosis regulation.