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

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Abstract
Summary: The effect of α interferon (α IFN) on colony forming unit, granulocyte‐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. αIFN (> 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 αIFN‐suppression is directly mediated. Morphological examination 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 αIFN selectively inhibits this compartment is relevant to the clinical effects of the cytokine in the disease.

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