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Early Decline in c-myb Oncogene Expression in the Differentiation of Human Myeloblastic Leukemia (ML-1) Cells Induced with 12-O-Tetradecanoylphorbol-13-acetate¹

Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, New York 14263

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 >50% as early as 3 hr after 12-O-tetradecanoylphorbol-13-acetate exposure, and at 8 to 72 hr the reduction was 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 marcrophage-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.

¹ Supported by Grant CA12585 from the National Cancer Institute.

Received 8/15/83. Accepted 10/25/83.

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