Differential expression of c-myc and c-fos oncogenes during the differentiation of human leukemic cells by Ara-C.

1-B-D-arabinofuranosyl cytosine (Ara-C) is, at very low concentrations, an inducer of monocytic differentiation of human leukemic cells. By what mechanisms this differentiation is obtained and how the monocytic pathway is determined, is not yet understood. We studied the effect of Ara-C on the RNA transcript levels of two c-oncogenes often associated to cell proliferation and differentiation. In the monoblastic U-937 cell line, where Ara-C has a maximum (100%) monocytic differentiation, RNA transcript level of c-myc is not detectable, whereas c-fos levels are rapidly increased. On the other hand, in the bipotential promyelocytic HL-60 cells, Ara-C induces only 40% monocytic differentiation after 7 days; this is associated to a weaker decrement of c-myc expression; c-fos is however greatly induced 3 log after 2 days treatment, but before monocytic phenotype is observed. Ara-C, at low concentrations, may, by arresting cell proliferation, restore the leukemic's cell proliferation/differentiation equilibrium. The rapid inducement of c-fos expression may allow to foresee a rapid prescreening of Ara-C sensitive-blasts.