Hematopoietic growth factors and marrow stroma in aplastic anemia.

An abnormal bone marrow microenvironment and hematopoietic growth factors are considered as one of the possible mechanisms of aplastic anemia. Circulating levels of erythropoietin, granulocyte colony-stimulating factor (G-GSF), granulocyte-macrophage colony-stimulating factor (GM-GSF) and thrombopoietin are significantly higher in patients with aplastic anemia than in normal controls. Of the two hematopoietic growth factors, acting at the early stages of hematopoiesis, circulating levels of flt-3 ligand are highly elevated in patients with aplastic anemia, whereas those of stem cell factor (SCF) are essentially normal. Decreased production has been described only for interleukin (IL) 1. This may reflect defective monocyte-macrophage maturation in patients with aplastic anemia. Marrow stromal cells are thought to exert a regulatory role in hematopoiesis, at least in part, by the production of certain hematopoietic growth factors. The abilities of stromal cells to produce hematopoietic growth factors, including G-GSF, GM-CSF, IL-6 and SCF, are either normal or elevated in the majority of patients. Thus, the deficiencies of hematopoietic growth factors are unlikely to be the cause of aplastic anemia.