Early decline in c-myb oncogene expression in the differentiation of human myeloblastic leukemia (ML-1) cells induced with 12-O-tetradecanoylphorbol-13-acetate.

The relationship of oncogene expression to proliferation and differentiation has been examined in a line of human myeloblastic leukemia (ML-1) cells. Proliferating leukemic cells were found to express a 4.3-kilobase cellular homologue (c-myb) of the transforming sequence of avian myeloblastosis virus. A rapid decline in the expression of this transcript was seen in cells induced to differentiate with 12-O-tetradecanoylphorbol-13-acetate. The level of c-myb RNA was decreased by greater than 50% as early as 3 hr after 12-O-tetradecanoylphorbol-13-acetate exposure, and at 8 to 72 hr the reduction was greater than or equal to 4-fold. Subsequent to the decrease in oncogene expression at 3 hr, DNA synthesis began to decline; by 24 hr, cell proliferation had ceased. At this time, monocyte- and macrophage-like cells were beginning to emerge. These findings demonstrate that c-myb is expressed during ML-1 cell proliferation and declines prior to the loss of DNA synthesis that accompanies the differentiation process.