Cooperative Regulation of c-myc Expression in Differentiation of Human Promyelocytic Leukemia Induced by Recombinant γ-lnterferon and 1,25-Dihydroxy vitamin D3¹

The biological activity of recombinant human γ -interferon (IFN-γ ) to induce the phenotypic differentiation of human promyelocytic leukemia cell line HL-60 and to regulate c-myc expression was evaluated. Treatment with IFN-γ increased monocyte-as-sociated cell surface antigens detected by monocyte-specific monoclonal antibodies in a dose- and time-dependent manner. These antigenic changes were accompanied by a functional differentiation, determined by the increase of phagocytic capability and superoxide generation. IFN-γ was also found to suppress the growth of HL-60 cells and reduce expression of a c-myc oncogene. These phenotypic and morphological changes to macrophage-like cells induced by IFN-γ were similar to those by 1,25-dihydroxyvitamin D₃, whereas the plasma membrane antigenic changes were different. Moreover, the combination of IFN-γ and suboptimal doses of 1,25-dihydroxyvitamin D₃ have synergistic effects in augmenting mature monocyte specific antigens (Mo2, 63D3, OKM1, and OKM5). In the reduction of c-myc expression by these drugs, a cooperative effect was observed with the inhibition of transferrin receptor expression and cell growth. These results indicate that human recombinant IFN-γ induces a monocyte phenotype in the HL-60 cells via a mechanism different from the action of 1,25-dihydroxyvitamin D₃.