Cytosine arabinoside phosphorylation and deamination in acute myeloblastic leukemia cells

Extracts of peripheral leukocytes from patients with AML and from controls were examined for enzymes involved in the metabolism of ara-C in order to investigate a possible relationship between enzymes activities and improvement of treatment with ara-C. The enzymes are deoxycytidine kinase and cytidine deaminase, which activates and inactivates ara-C respectively. Cytidine deaminase activity was found to be lower in AML cells than in normal cells, while deoxycytidine kinase was higher in AML cells. Furthermore, the ratio between kinase activity with ara-C as substrate and activity with deoxycytidine as substrate was higher in AML cells than in normal leukocytes. However, there was no significant difference between those patients with AML, who respond to ara-C treatment, and the patients who did not respond.The enzymatic differences between normal and AML leukocytes with regard to activity and substrate specificity might suggest that ara-C could be combined with advantage with deoxycytidine in the clinic.