Interferon Regulation of Differentiation and Mechanisms

The clear involvement of the interferon (IFN) system in the regulation of differentiation justifies the advanced IFN clinical trials in “differentiation therapy” of cancer. By employing this strategy, it may be possible to specifically reprogram the phenotype of a tumor cell by inducing its terminal cell differentiation and, thus, the loss of its tumorigenic potential. The effects of IFNs on erythroid differentiation and the related mechanisms are reported. Administration of highly purified preparations of murine IFN-alpha or -beta to Friend leukemia cells, induced to differentiate by dimethyl-sulfoxide, leads to a 100% increase of benzidine-positive cells. Both species of IFN induce a substantial increase in heme, hemoglobin and transferrin receptor levels. The results obtained suggest that in erythroid cells the intracellular heme level may represent a key regulatory factor in the hemoglobin synthesis pathway. It is postulated that IFN induces the enhancing effect on differentiation via a marked increase of heme synthesis and number of transferrin receptors which in turn leads to an enhancement of globin chain synthesis.