Induction of the pro-myelocytic leukaemia gene by type I and type II interferons

THE physiological role of the pro-myelocytic leukaemia (PML) gene product i s poorly defined. Among other functions, PML. is involved in haematopoietic differentiation and in control of cell growth and tumorigenesis. We invest igated the regulation of human PML expression by interferons (IFNs) and IL- I in various human haematopoietic lines (U937, THP1, HL60, NB4), in human d iploid fibroblasts and in human peripheral blood leukocytes, Cytokine-induc ed modulation of PML expression was assessed by Northern blot analyses, flo w cytometry studies and in situ immunolabelling. Our data show that IFNs an d IL-1 upregulate PML transcript and protein expression in a time and dose- dependent manner. In situ immunolabelling revealed that upregulation of pro tein expression by IFN-alpha is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodie s. Our data suggest that stimulation of PML expression by interferons and I L-1 may account for upregulation of PML proteins observed in inflammatory t issues and in proliferative states.