Antileukemic efficacy of 2 '-deoxycoformycin in monocytic leukemia cells

2'-Deoxycoformycin (dCF) as a single agent has been reported to be less eff ective against myeloid than against lymphoid malignancies in clinical trial s. However, previous studies have shown that in the presence of 2'-deoxyade nosine (dAd), human monocytoid leukemia cell lines are much more sensitive to dCF with regard to the inhibition of cell proliferation, Thus, dCF might be useful for treating monocytoid leukemia with the aid of dAd analogs. Th e antiproliferative effects of dCF in combination with dAd or its derivativ es were examined on normal and malignant blood and bone marrow cells. In th e presence of 10 mu mol/L dAd, the concentration of dCF required to inhibit the viability of primary monocytoid leukemia cells was much lower than tha t required to inhibit normal or non-monocytoid leukemic cells. Among the dA d analogs, 9-beta-D-arabinofuranosyladenine (AraA) was also effective in co mbination with dCF, Athymic nude mice were inoculated with human monocytoid leukemia U937 cells and treated with dCF or a dAd analog or both, Although dCF alone slightly but significantly prolonged the survival of mice inocul ated with U937 cells, combined treatment with dCF and AraA markedly prolong ed their survival. These data suggest that the combination of dCF and AraA may be useful for the clinical treatment of acute monocytic leukemia. (Bloo d. 2000;96:1512-1516) (C) 2000 by The American Society of Hematology.