A novel therapeutic strategy against monocytic leukemia with deoxyadenosine analogs and adenosine deaminase inhibitors

The adenosine deaminase inhibitor 2'-deoxycoformycin (dCF) significantly in hibits the proliferation of leukemia and lymphoma cells in the presence of either 2'-deoxyadenosine (dAdo) or its analog adenine arabinoside (araA). T he concentration of dCF required to induce apoptosis of monocytoid leukemia cells is much lower than that required for myeloid, erythroid, or lymphoma cells. dATP effectively induces caspase-3 activation in cytosol from monoc ytoid cells, but not in that from non-monocytoid cells, suggesting that dAT P-dependent caspase-3 activation is involved in the preferential induction of apoptosis in monocytoid leukemia cells. Athymic nude mice inoculated wit h human monocytoid leukemia U937 cells show significantly prolonged surviva l following combined treatment with dCF and araA- The clinical usefulness o f the combination of adenosine deaminase inhibitor and dAdo analog is discu ssed.