Mechanism of action of α interferon in chronic granulocytic leukaemia: evidence for preferential inhibition of late progenitors

Abstract

The effect of .alpha. interferon (.alpha. IFN) on colony forming unit, graunlocyte-macrophage (CFU-GM) formation by normal bone marrow(BM) as compared with chronic granulocytic leukaemia (CGL) BM and peripheral blood (PB) was tested in semi-solid assay systems employing either 5637CM or recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) to support growth. .alpha.IFN (> 125 U/ml) caused consistent inhibition (P = 0.02) of day-7 (late progenitor) colonies, but had little or no effect on either day-7 clusters or day-14 colonies/clusters. This selective effect on day-7 colonies was quantitatively similar for both normal and CGL (p > 0.5). Similar results were obtained whether or not the mononuclear preparations were depleted of potential accessory cells, suggesting that the .alpha.-IFN-suppression is directly mediated. Morphological examinations of colonies and clusters showed that IFN had no effect on cell maturation and that colony inhibition is not, therefore, a consequence of blocked maturation. Since the late-progenitor compartment is preferentially expanded in CGL, we suggest that our demonstration that .alpha.-IFN selectively inhibits this compartment is relevant to the clinical effects of the cytokine in the disease.