ABSTRACT

Granulocyte-macrophage colony-stimulating factor (GM-CSF) holds a preeminent place in the history of cytokines, having been one of the first to be described, purified, cloned, and finally established as a clinically useful therapeutic agent. In this review, the biochemistry, molecular biology, genetics, and distribution of GM-CSF and its receptor will be outlined. The evidence supporting a contribution of GM-CSF to the pathogenesis of leukemia and other disease states will be discussed in the light of both transgenic and gene inactivation studies. The distribution of receptors for GM-CSF in normal cells includes myeloid progenitor cells, neutrophils, dendritic cells, monocytes, and eosinophils, but not lymphocytes or erythroid cells. The initial identification of GM-CSF was based on its ability to stimulate the in vitro proliferation and differentiation of hematopoietic progenitors to granulocytes and macrophages. The ready availability of both human and murine cell lines able to respond to GM-CSF has facilitated many experiments undertaken in the field of hematopoietic cell biology.