The role of growth factors in haemopoietic development: clinical and biological implications.

Abstract

Mature blood cells of all lineages are derived from a single class of cell, the haemopoietic stem cell. Stem cells are pluripotent and capable of almost limitless self-renewal. In the bone marrow they form part of a hierarchy that includes progenitor cells, which are more restricted in the lineages their progeny can adopt, and precursor cells, which are committed to differentiation. The mechanisms that regulate progression through this hierarchy are not fully understood, but evidence suggests that both bone marrow stromal cells and soluble growth factors have a role in controlling haemopoiesis. Four growth factors act on progenitor cells to promote their survival, proliferation, differentiation, and maturation: interleukin-3 (IL-3), granulocyte/macrophage-colony stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF). They can also activate the function of mature cells. Considerable overlap is found in the target cells for these four growth factors. We have found that growth factors acting in synergy can recruit more primitive cells than had previously been appreciated. These factors can also determine the lineage that the progeny of multipotential progenitors will adopt. Thus, colony-stimulating factors (CSFs) have the potential to regulate the development of primitive haemopoietic cells in vivo. The properties of CSFs have made them useful in treating malignant disease: G-CSF, in particular, has been used to reduce the period of neutropaenia that follows cytotoxic therapy for various malignancies. The success of these early trials gives ground for cautious optimism about the clinical use of these compounds.