12-o-tetradeca-2-4-6-8-tetranoylphorbol-13-acetate and Leukemia

Topics: Bone Marrow Cells; Cell Transformation, Neoplastic; Cells, Cultured; Fibroblast Growth Factors; Hematopoiesis; Hematopoietic Stem Cells; Humans; Leukemia; Tetradecanoylphorbol Acetate

Topics: Acute Disease; Adolescent; Adult; Cell Transformation, Neoplastic; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Leukemia; Male; Middle Aged; Tetradecanoylphorbol Acetate

In the present study, the expression of beta-adrenergic receptors, the activity of the enzyme adenylate cyclase (AC), and the intracellular concentration of cyclic adenosine 3',5'-monophosphate (cAMP) were investigated in HL-60 cells before and after their differentiation to monocytic or more mature granulocytic cells. Treatment of the HL-60 promyelocytes with 12-O-tetradecanoylphorbol 13-acetate or human interleukin 2 resulted in the appearance of cells with monocytic characteristics (morphology, non-specific esterase, adherence, reaction with a monocyte-specific monoclonal antibody). Induction with retinoic acid resulted in differentiation to cells with typical features of mature granulocytes (morphology, peroxidase, nitro-blue tetrazolium reduction). During maturation to monocytes, the density of beta-adrenergic receptors decreased, whereas it remained constant during maturation to granulocytes. In comparison with normal circulating monocytes or polymorphonuclear granulocytes, expression of beta-adrenergic receptors on the surface of the differentiated HL-60 cells was low. Activation of AC by the hormones isoproterenol, prostaglandin E1, and histamine generally decreased with HL-60 maturation and enzyme activities were markedly below those measured in normal peripheral leukocytes. In the induced monocytic HL-60 cells, the weak effectiveness of isoproterenol was due to the loss of beta-adrenergic receptors. In the induced granulocytic HL-60 cells, the reduced hormonal AC activation could be explained by the impaired coupling between hormone receptors and catalytic enzyme unit. The concentration of intracellular cAMP after differentiation of HL-60 cells reflected the increase in basal AC activity and the decrease in hormone stimulation of the enzyme. Our data indicate that HL-60 cells induced to differentiate possess some monocyte- and granulocyte-like properties, but do not meet several important functional criteria of their new cell identities.

Topics: Adenylyl Cyclases; Cell Differentiation; Cell Line; Cyclic AMP; Granulocytes; Humans; Leukemia; Monocytes; Receptors, Adrenergic; Receptors, Adrenergic, beta; Tetradecanoylphorbol Acetate; Tretinoin