The differentiation, proliferation, and viability of hemopoietic cells are regulated by glycoproteins variously referred to as colony-stimulating factors (CSFs), growth factors, or hemopoietins. To date, 12 interleukins, 3 CSFs, erythropoietin, and a stem cell growth factor (kit ligand, or mast cell growth factor) are known to regulate hemopoiesis. The identification and purification of human hemopoietic growth factors (cytokines) have recently permitted a more detailed analysis of their role in hemopoiesis. Cloning of the genes that encode these CSFs has led to largescale production of their protein products for clinical application. Recent clinical trials of these cytokines in adults and children with a variety of diseases affecting hemopoiesis have already yielded dramatic benefits. For example, patients with formerly serious or fatal diseases, such as cyclic neutropenia or Kostmann syndrome (congenital agranulocytosis), have shown striking reductions in infections, marked improvement in their quality of life, and no serious side effects during treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF).
Here we summarize what is known about the biology and clinical utility of five of these CSFs (recombinant human erythropoietin [rh-EPO], rhG-CSF, granulocyte-macrophage colony-stimulating factor [rhGM-CSF], macrophage colony-stimulating factor [rhM-CSF], and interleukin-3 [rhIL-3]), which are in clinical use in children. We also indicate future applications for these and other hemopoietins. Table 1 outlines characteristics of the five agents, and Table 2 lists their clinical applications.
HEMOPOIETINS AND HEMOPOIESIS
Hemopoiesis is a complex and dynamic process during which a relatively small number of stem cells with self-renewal capacity give rise to lineage-restricted progenitor cells that mature into red blood cells, leukocytes (white blood cells), or platelets (see Figure).
Convergence of signaling by interleukin-3, granulocyte-macrophage colony-stimulating factor, and mast cell growth factor on JAK2 tyrosine kinase.