CHARACTERIZATION OF A CELL-TYPE-RESTRICTED NEGATIVE REGULATORY ACTIVITY OF THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENE

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimul ates the proliferation and maturation of normal myeloid progenitor cel ls and can also stimulate the growth of acute myelogenous leukemia (AM L) blasts. GM-CSF is not normally produced by resting cells but is exp ressed by a variety of activated cells including T lymphocytes, macrop hages, and certain cytokine-stimulated fibroblasts and endothelial cel ls. production of GM-CSF by cultured AML cells has been demonstrated, and GM-CSF expression by normal myeloid progenitors has been postulate d to play a role in myelopoiesis. We have investigated, the regulation of expression of GM-CSF in AML cell lines and our results demonstrate the presence of a strong constitutive promoter element contained with in 53 bp upstream of the cap site. We have also identified a negative regulatory element located immediately upstream of the positive regula tory element (within 69 bp of the cap site) that is active in AML cell lines but not T cells or K562 CML cells. Competition transfection and mobility shift studies demonstrate that this activity correlates with binding of a 45-kDa protein.