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 (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulted in a sharp increase in 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 10(2)-10(5) U/ml of the three IFN subtypes. In self-renewal assays derived from the primary cultures that initially contained IFN alpha 2, a "carryover" antiproliferative effect was observed with a dose-dependent decline in secondary growth. In comparison studies of IFN alpha-A and IFN alpha-C, the suppressive effect on primary myeloblast growth was much more pronounced with IFN alpha-C at concentrations of 10(3) U/ml and higher; in self-renewal assays, the antiproliferative effect of IFN alpha-C on secondary growth was no longer observed, whereas that of IFN alpha-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.
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D003114:Colony-Forming Units Assay; D004274:DNA, Recombinant; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000473:pathology*; D008297:Male
D004274:DNA, Recombinant; D007370:Interferon Type I; D015088:2',5'-Oligoadenylate Synthetase