Relationship between activities of key enzymes of Ara-C metabolism and clinical efficacy in children with hematopoietic malignancies

Objective To study the relationship between the expression of key enzymes of Ara-C metabolism and the outcome of acute leukemia and non-Hodgkin lymphoma in children via detecting deoxycytidine kinase(DCK)and cytidine deaminase(CDA)kinase activity.Methods ~3H-Cytidine was used to detect DCK and CDA activity from 19 leukemia patients with acute lymphoblastic leukemia(ALL),9 patients with acute myeloid leukaemia(AML) and 4 patients with non- Hodgkin lymphoma leukemia(NHL).Results The enzyme activity of DCK in the newly diagnosed patients was significantly higher than that in the relapsed cases.But the enzyme activity of CDA in the new diagnosed patients of the study group was significantly lower than that in the relapsed cases.The similar results were also observed in the two groups when compared clinical outcome with the ratio of CDA and DCK.There was no difference of the enzyme activity of DCK in different types of new diagnosed patients(ALL,AML,NHL).There was no correlations among enzyme activity,age,and sex.Conclusion Increasing DCK activity can promote Ara-C metabolism to Ara-CTP,but enhancing CDA activity can accelerate Ara-C degradation with interfering clinical efficacy.The results in the study showed that the lower expression of DCK and higher expression of CDA may be the reasons for relapse patients.Thus,there is a strong correlationship between the expression of DCK and CDA with the clinical outcome of hematopoietic malignancies in children.