SYNERGY BETWEEN SCF OR M-CSF WITH IL-3 OR GM-CSF IN FDC-P1 CELLS - A SENSITIVE ASSAY OF TRANSFORMING MUTATIONS OF C-FMS

Stem cell factor (SCF) was found to stimulate the growth of the haemop oietic cell line FDC-P1 in synergy with either Interleukin 3 (IL-3) or granulocyte-macrophage-colony stimulating factor (GM-CSF). Similarly, macrophage colony-stimulating factor (M-CSF) was shown to synergize w ith IL-3 or GM-CSF, following the Infection of FDC-P1 cells with a rec ombinant retrovirus which encoded the receptor far M-CSF (M-CSFr). The se results raise the possibility that signal transduction pathways whi ch are controlled by SCF in FDC-P1 cells, can be activated by M-CSF if its receptor is illicitly expressed. FDC-P1 cells that expressed the M-CSFr were responsive to as little as 100 U/ml of M-CSF when added in combination with IL-3 or GM-CSF. This sensitive assay was used to dem onstrate that transforming deletions of the C-terminal tail of the M-C SFr and two-point mutations within the same region that converted tyro sine 969 to either phenylalanine or to cysteine, allowed the mutant M- CSF receptors to synergize with IL-3 or GM-CSF in the absence of M-CSF . These mutations were found to be more evidently transforming in FDC- P1 cells than in Rat-2 fibroblasts. The possible relevance of these re sults to leukaemia and to gynaecological malignancies is discussed.