Hematopoietic growth factors.

Abstract

The process of blood cell formation, by which a small number of self-renewing stem cells give rise to lineage committed pro- genitor cells that subsequently proliferate and differentiate to produce the circulating mature blood cells, is sustained through- out life by a group of glycoprotein hormonal growth factors.These hormones are known collectively as the colony-stimulating factors (CSFs)' (1); the term derives from the in vitro observation that the CSFs stimulate progenitor cells of different hemato- poietic cell lineages to form discrete colonies of recognizable maturing cells.The different factors have been operationally de- fined by prefixes denoting the major type of colony produced, e.g., granulocyte maprophage CSF (GM-CSF).Not only is the presence of CSF5 necessary for the proliferation of progenitor cells but these factors affect the function of mature cells as well (2-8); furthermore, they may be the major regulators ofincreased cell production during states of increased demand.It is not yet clear whether they play a pathogenetic role in some forms of leukemia.During the past few years, the genes for five murine and human factors have been cloned, and recombinant forms ofthe proteins produced and purified.The recombinant CSFs have similar actions to their natural counterparts.The prospect of their availability in large quantities has provided the impetus for intensive investigation into their actions, to identify circumstances in which they may be therapeutically useful.The he- matopoietic system with its regulators also serves as a paradigm for other systems with self-renewing stem cell populations sustaining the production ofboth shortand long-lived mature cells.Types ofCSF Recent data on the biological activities ofseveral highly purified recombinant hormones have led to the appreciation that the existing nomenclature is inadequate.For example, although hu- man GM-CSF was initially described as a factor stimulating production ofgranulocyte and/or macrophage colonies, it is now Receivedfor publication 16 October 1986.