Differences in beta-adrenergic receptor density and adenylate cyclase activity between normal and leukaemic...

An identical class of high-affinity binding sites for the 125I-labelled beta-adrenergic antagonist hydroxybenzylpindolol, was identified on intact human normal and leukaemic peripheral blood leukocytes. On normal unfractionated lymphocytes, polymorphonuclear leukocytes, and monocytes, receptor density did not differ significantly (1200-1400 receptors per cell; P greater than 0.3), but it was higher on B- than on T-lymphocytes (P less than 0.05). In leukaemia, monocytic blast cells expressed highest receptor numbers, whereas very low receptor density was seen on the pathologic B-cells from chronic lymphocytic leukaemia. Among normal leukocytes, adenylate cyclase activation by hormones (isoproterenol, prostaglandin E1, histamine) and sodium fluoride was strongest in plasma membranes from monocytes, but very weak in polymorphonuclear leukocytes either due to uncoupling of hormone receptors from adenylate cyclase or to low catalytic activity. In T-cells, enzyme activity was significantly lower than in B-cells. Loss of adenylate cyclase sensitivity to hormones and fluoride occurred in leukaemic cells from chronic and acute lymphocytic leukaemia.