Analyses of Cyclic Nucleotide Phosphodiesterases in Lymphocytes from Normal and Aged Leukemic Mice1

The activity of cyclic 3 :5 -nucleotide phosphodiesterase was measured in thymocytes and splenic lympho cytes of AKR mice of various ages. Concurrently, the cell distribution profiles of these cell populations were studied by laser cytometric analysis. The results indicate that lymphocyte and thymocyte populations from young, con trol animals are relatively homogeneous with respect to cell size, whereas cell populations from old, leukemic mice showed increases in the percentage of larger, blastlike cells. These latter cell populations also showed in creases in cyclic nucleotide phosphodiesterase activity when compared with that of young animals. Old, nontumor-bearing mice had lower levels of enzyme activity than did their leukemic counterparts and showed only modest increases in the percentage of blast-like cells. Correlation analyses revealed that increases in enzyme activity correlated with increases in the percentage of large cells but not with increases in thymus weight. These data suggest that increases in phosphodiesterase activity are associated with the appearance of leukemic cells and not with a putative preleukemic state. Preparative polyacrylamide gel electrophoresis re vealed multiple forms of both cyclic adenosine and cyclic guanosine 3 :5 -phosphodiesterases. The pattern of the Phosphodiesterases showed distinct differences between normal and leukemic thymocytes. The major differences were a reduction in the more slowly migrating forms and a large increase in the activity of one form of the enzyme in the leukemic cells. This suggests that selective inhibition of this form of phosphodiesterase might be effective therapy for certain types of leukemias.