DOWN-REGULATION OF C-MYC GENE IS NOT OBLIGATORY FOR GROWTH-INHIBITIONAND DIFFERENTIATION OF HUMAN MYELOID-LEUKEMIA CELLS

Suppression of c-myc expression is observed during induced differentia tion of several myeloid cell lines and it has been attributed to the c ell growth arrest that accompanies terminal differentiation. To dissec t the role of c-Myc in the proliferation-differentiation switch we hav e studied c-myc expression in K562 cells exposed to several chemical a gents. This model system allowed us to discriminate between the growth arrest and differentiation phenomena as well as the induction of diff erentiation along two different lineages (erythroid and myelomonocytic ). Our results showed that c-myc expression did not significantly decr ease when growth inhibition is reversible, either by treatment with a differentiating agent such as hydroxyurea (which induced erythroid dif ferentiation) or by a non-differentiating agent such as interferon-alp ha. In contrast, c-myc expression decreased when cells underwent termi nal differentiation, either along the myelomonocytic (by 12-O-tetradec anoylphorbol-13-acetate) or erythroid (by 1-beta-D-arabinofuranosylcyt osine) lineages. These results indicated that c-myc down-regulation is not obligatory for growth arrest and non-terminal differentiation of human myeloid cells. In contrast, c-myc down-regulation occurred in te rminal differentiation, but induction of myelomonocytic differentiatio n resulted in a greater loss of c-myc mRNA than induction of erythroid differentiation.