THE GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR (GM-CSF) - BASIC SCIENCE AND CLINICAL-APPLICATION

Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) stimulates the production as well as the function of myeloid cells, i.e. granulocytes and macrophages. Proliferative effects are exerted on the level of the multipotent as well as the unipotent progenitor cell. Functional effects on mature phagocytes comprise bactericidal and tumoricidal mechanisms including induction of cytokine release. GM-CSF receptors are present on normal hematopoietic progenitors as well as on mature granulocytes, on leukemic cells and some non-hematopoietic cells. Alteration of the GM-CSF gene has been associated with distinct features of AML and ALL. The glycosilated molecule is produced by various hemolymphopoietic and possibly non-hematopoietic cells, amongst whom T-lymphocytes and marrow stroma may be most relevant for myelopoiesis. The regulation of gene expression is exerted on both transcriptional and posttranscriptional levels of gene expression. GM-CSF production may play a role in steady state as well as in stress hematopoiesis. In vivo application of GM-CSF leads to a marked increase of phagocytes, in particular granulocytes. GM-CSF reduces the duration of neutropenia following aplasiogenic and ablative therapy. GM-CSF may possibly be helpful in the treatment of victims of radiation accidents and in patients with aquired neutropenias and glykogenosis IB. The curative potential for the underlying malignant disease is to be investigated in the present cooperative european Ewing's sarcoma study.