Phorbol Ester Effect on Differentiation of Human Myeloid Leukemia Cell Lines Blocked at Different Stages of Maturation

The control of differentiation by tumor-promoting phorbol diesters including 12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated using cells from human myeloid leuke mia lines and sublines that were blocked at different stages of maturation. The myeloid leukemia cells that were blocked at the myeloblast-promyelocyte stage of maturation (KG-1, HL- 60, and ML-3) had a prominent response when cultured withTPA. The cells became adherent, developed pseudopodia, displayed macrophage characteristics by light microscopy, developed nonspecific acid esterase activity, phagocytized yeast, slightly reduced nitro blue tetrazolium, displayed Fcimmunoglobulin G receptors, and killed bacteria. Lysozyme secretion and enzyme activity for ß-glucuronidase and acid phosphatase increased 2- to 20-fold concomitant with macro phage differentiation. The myeloid leukemia cells that were blocked at the undifferentiated myeloid blast stage of maturation (KG-1 a and K562) were completely resistant to TPA-induced macrophage differentiation. We examined ten macrophage functions in the myeloid cell lines and sublines after exposure to phorbol diesters. The leukemic lines blocked at the myeloblast-promyelocyte stage of maturation expressed almost all the macrophage-specific functions. Phorbol diesters probably induced differentiation through a common cellular mechanism because the macrophage-differentiated events could not be dissociated. In sharp contrast, the early myeloid blast cells (KG-1 a and K562) were incapable of acquiring any of the macrophage-specific functions after exposure to phorbol diesters. The KG-1 a variant, in particular, should provide a good model to help elucidate the regulatory mechanism controlling the expression of macro phage functions during exposure to phorbol diesters.