We are continuing to study regulatory events in early hematopoiesis in humans. In addition to establishing assays in culture for human pluripotent stem cells, we have now applied the techniques of recombinant DNA technology to isolate hematopoietic growth factors. Specifically, we have cloned and expressed the gene for human granulocyte/macrophage colony stimulating factor (GM-CSF) and human erythropoietin. A variety of antibodies to these growth factors are being developed using material purified from expression systems. The goal of this portion of the work is to distinguish between pathway-specific factors for granulopoiesis and erythropoiesis. Using expression system assays, we are also attempting to clone the gene for a human multilineage colony stimulating factor (multi-CSF). Antibodies developed to the various factors will be used to assess their role in vivo. In studies in humans with various diseases, we are comparing and quantitating mechanisms of hematopoietic regulation, particularly in myeloproliferative syndromes. These include the response in vivo and in vitro of erythroid colony-forming cells to changing levels of erythropoietin. We are also using antibodies to the hematopoietic growth factors to assay levels of these factors in patients with various forms of marrow failure following chemotherapy and bone marrow transplantation. Through these studies we hope to learn more about the regulatory interactions which influence the phenotypes of the myeloproliferative syndromes in man. (J)
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