Features of the initial metabolism of 1-beta-D-arabinofuranosylcytosine in human myeloid leukemic cells.
With the aim of improving the treatment of AML patients the activities of selected nucleoside metabolizing enzymes of possible implication for the initial metabolism of Ara-C have been studied in leukemic and normal cells. An increased ADA activity, a slightly changed PNP activity, a decreased CDD activity and an increased dCK activity, including deviation in substrate specificity, were found in myeloid leukemic cells. The increase of ADA may in part be related to immaturity of the cells. This is supported by the finding of a decrease in the ADA activity during experimental induced differentiation of myeloid cells. On the other hand differentiation is not dependent on the ADA decrease, since differentiation can occur without the decrease of ADA. The correlation between myeloid blast counts in peripheral blood from AML patients and the ADA activity also supports the connection between the development stage of the cells and the ADA activity. Minor changes of the ADA activity in myeloid cells from patients with liver cirrhosis have been observed without changes in the maturity of the cells indicating that other factors than the differentiation of the cells are of importance for the activity of ADA in myeloid cells. Only minor changes have been observed in the activity of PNP related to myeloid leukemic cells. CDD activity is decreased in myeloid leukemic cells. Differentiation is probably of major importance for the activity, experimentally supported by the increase observed concurrently with induced differentiation of myeloid cells. An inverse correlation between the CDD activity and the blast counts in patients with AML is also supportive.(ABSTRACT TRUNCATED AT 250 WORDS)
Mejer
J N
JN
Medical Department C, Bispebjerg Hospital, Copenhagen.
D003561:Cytarabine / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology
D003561:Cytarabine