Effects of 12-O-TetradecanoylphorboM 3-acetate on the Proliferation and Differentiation of Normal and Leukemic Myeloid Progenitor Cells1

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on myeloid colony formation were investigated by initial and delayed addition of TPA to the cultures. In the human placental condi tioned medium-stimulated cultures, TPA inhibited normal myeloid colony formation without any change in colony morphology when added at the beginning of culture. However, macrophage-like transformation of myeloid colonies by TPA was clearly observed after the delayed addition of TPA. Colonies and clusters already formed at the time of TPA addition were exclusively neutrophilic. Two days after TPA addition, many colonies apparently con tained macrophage-like cells. Within 4 days after TPA addition, almost all myeloid colonies transformed into the macrophage type. Parallel study of initial and delayed addition of TPA revealed that this macrophage-like transformation of neutrophilic colonies occurred at high concentrations of TPA that would fully inhibit colony formation if added initially. TPA caused similar effects on leukemic colony formation.