Regulation of gene expression of adenosine deaminase, purine nucleoside phosphorylase and terminal deoxynucleotidyl transferase by dexamethasone and cAMP in human leukemic cells.

Inherited deficiencies of enzymes in the purine catabolic pathway, 5’-Nucleotidase (5’-NT), Adenosine Deaminase (ADA), Purine Nucleoside Phosphorylase (PNP) have been associated with states of immunodeficiency.1-3 These enzymes change during lymphoid cell differentiation, ADA activity is higher in immature cells, while PNP and 5’-NT activities are lower.4 As the lymphoid cells differentiation proceeds, ADA activity decrease, and PNP and 5’-NT activities increase, which has established the importance of purine metabolism in the immune system.5 On the other hand, Terminal Deoxynucleotidyl Transferase (TdT) is DNA pol, which catalyse the addition of deoxynucleotides in absence of a template.6 TdT activity is restricted to immature lymphoid cells.7 It has been proposed that TdT plays an important role in the generation of diversity of Immunoglobulins and T-cell antigen receptor molecules during gene rearrangements.8’9 These observations led the postulation these enzymes may play a role in lymphocyte differentiation,10 and led to the idea that in early lymphoid cells, 5’-NT, ADA and PNP regulate intracellular deoxynucleoside triphosphate pool, which are substrates of TdT.11 Thus, the expression of ADA, PNP and TdT genes may be coordinately regulated during lymphoid cell differentiation. We shown that PKC activation regulates the gene expression of ADA, PNP and TdT in normal lymphoid and leukemic cells.12-13 To further test which other intracellular signals regulate the expression of ADA, PNP and TdT in undifferentiated malignant cells, we studied the role of cAMP and Dexamethasone in the regulation of gene expression of these enzymes.