Cyclases In Normal And Leukemic Lymphocytes

Persistent low level of c-AMP and persistent high level of cGMP in leukemic lymphocytes suggest a modified activity of the cyclases which synthetize them. Soluble and particulate guanylate cyclase (GC) and adenylate cyclase (AC) activities were studied in normal B-enriched and T-enriched lymphocytes, in lymphocytes of children with acute lymphocytic leukemia (ALL) and adults with chronic lymphocytic leukemia (CLL). GC activity was greater in normal T than B cells (10.2 vs 5.3 pmol/min/mg protein), increased little with isoproterenol and prostaglandins stimulation, and much more with sodium azide (NaN3) and dehydroascorbic acid (DHA) stimulation (19 and 23 pmol for T cells and 9.1 and 17.2 pmol for B cells). GC activity was greater in both types of leukemic lymphocytes (23 pmol for ALL cells and 18 pmol for CLL cells) and was insensitive to stimulation with DHA and NaN3. Particulate AC activity was greater in normal B than T cells (215 vs 80 pmol) and increased in both after stimulation with isoproterenol (300 pmol) and prostaglandins (400 pmol). In leukemic lymphocytes AC showed depressed activity (20 pmol in ALL cells and 55 pmol in CLL cells) and was insensitive to stimulation. These findings suggest that circulating T cells are more actively cycling or functioning than circulating B cells. They also suggest a derangement of the activity of both cyclases and/or their receptors in leukemic cells: this derangement may be a cause of leukemic cell escape from their microenvironment control.