THE COMBINED EFFECTS OF IL-3, GM-CSF AND G-CSF ON THE INVITRO GROWTH OF MYELODYSPLASTIC MYELOID PROGENITOR CELLS

The decreased or absent in vitro colony formation in response to single recombinant haematopoietic growth factors has been reported previously. Here we report on the effects of the combination of interleukin 3 (Il-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) and the effect of the conditioned medium of the giant tumour cell line (GCT-CM) on the proliferation of myelodysplastic (MDS) marrow myeloid progenitor cells and normal bone marrow (NBM) controls. Colony growth was most effectively sustained by GCT-CM and G-CSF in normal bone marrow (NBM) cultures. GM-CSF and Il-3 were less effective in inducing myeloid granulocytic colony growth, whereas the effects of Il-3 and GM-CSF were found to be approximately additive. The number of NBM granulocytic colonies induced by G-CSF and GCT-CM stimulation were comparable, whereas this granulocyte colony stimulating activity could be neutralized by anti-G-CSF antibodies. In addition GCT-CM was found to contain burst promoting activity, which could be neutralized by anti-Il-3 antibodies. Il-3 did not enhance the G-CSF activity in NBM cultures. No additive effect of stimulation with the combination of Il-3 and GM-CSF was observed in MDS marrow cultures, suggesting that these growth factors act on an identical progenitor cell population in MDS. G-CSF stimulated the growth of significantly lower colony numbers than GCT-CM, in contrast to NBM cultures. The decreased granulocytic colony formation of MDS marrow cells could clearly be enhanced by co-stimulation with Il-3. These results suggest that MDS myeloid progenitor cells require the exposure to both a pluripotent colony stimulating factor, like Il-3, and a lineage specific factor, like G-CSF, for optimal proliferation.