Dose-dependent effects of a tumor promotor on blast cell progenitors in human myeloblastic leukemia

AML blast cell progenitors form colonies in culture when stimulated by a media conditioned by leukocytes in th presence of PHA. Two cellular processes occur during colony formation: self renewal generates new progenitors, while others undergo a change that leads to decreased proliferative potential. We tested the effect of the potent tumor promotor, 12-0-tetradecanoyl phorbol acetate (TPA) on these events. TPA was found to be toxic to blast cell colony formation; doses in excess of 1 ng per ml usually abolished it. At doses lower than this, self renewal, as determined by replating either individual or pooled colonies, was increased. At proliferation inhibiting TPA doses, surviving cells showed a spindle morphology, and had increased ANA esterase activity. We interpret the data to mean that TPA decreases blast cell maturation at low doses and may increase it at high doses.