Increased ratio between deoxycytidine kinase and thymidine kinase 2 in CLL lymphocytes compared to normal lymphocytes.
Deoxycytidine kinase (dCK) is important in the 5'-phosphorylation of deoxynucleoside analogs. Like dCK, thymidine kinase 2 (TK2) catalyzes the initial step of the phosphorylation of dcyd to dCTP. Thymidine is a strong inhibitor of the dCK activity of TK2. We examined the ratio of the dcyd phosphorylation carried out by dCK and by TK2 (dCK/TK2-dcyd) in lymphocytes from CLL patients and from donors. In the CLL lymphocytes we found a 3.5-fold average increase. Therefore, we conclude that addition of thymidine in the treatment of CLL with deoxynucleoside analogs will not be of any advantage. Furthermore, our results can explain earlier findings in CML and AML lymphocytes where the ara-C phosphorylation was twice the dcyd phosphorylation.
Nielsen
S E
SE
Department of Hematology and Oncology, Roskilde Hospital, Denmark.
Munch-Petersen
B
B
Mejer
J
J
D002478:Cells, Cultured; D017338:Cladribine / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000378:metabolism*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology*; D010766:Phosphorylation; D013379:Substrate Specificity; D013937:Thymidine Kinase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017338:Cladribine; D013937:Thymidine Kinase; D003842:Deoxycytidine Kinase