Growth inhibitory effect of gene-cloned interferons on human myeloblast colonies

The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFNα₂, IFNα-A, and IFNα-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFNα resulted in a sharp increase ih the IFN-induced enzyme 2-5A synthetase, indicating the expression of IFN cell receptors as well as the ability of leukemia cells to respond metabolically. Dose-response studies showed a dose-dependent suppression of myeloblast colony formation in all experiments using concentrations of 10²-10⁵ U/ml of the three IFN subtypes. In self-renewal assays derived from the primary cultures that initially contained IFNα₂, a 'carryover' antiproliferative effect was observed with a dose-dependent decline in secondary growth. In comparison studies of IFNα-A and IFNα-C, the suppressive effect on primary myeloblast growth was much more pronounced with IFNα-C at concentration of 10³ U/ml and higher; in self-renewal assays, the antiproliferative effect of IFNα-C on secondary growth was no longer observed, whereas that of IFNα-A persisted. These three subtypes of gene-cloned IFN have antileukemic properties in vitro, with differences in degree of suppression of primary myeloblast growth and of self-renewal.