GROWTH FACTORS IN NORMAL AND NEOPLASTIC HEMATOPOIESIS

我们正在继续研究早期造血中的调节事件。 人类。除了在培养中为人类建立检测方法之外 多能干细胞，我们现在已经应用了重组技术 利用DNA技术分离造血生长因子。具体来说，我们 克隆并表达了人粒细胞/巨噬细胞集落形成基因 刺激因子和人促红细胞生成素。各种各样的 针对这些生长因子的抗体是用材料开发的 从表达系统中提纯。这部分工作的目标是 为了区分粒细胞生成的途径特异性因子和 红血球生成。利用表达系统分析，我们还试图 克隆人多系集落刺激因子基因 (多个脑脊液)。针对各种因素开发的抗体将被用于 评估它们在体内的作用。 在对患有各种疾病的人类进行的研究中，我们正在比较和 造血调节的量化机制，特别是在 骨髓增殖性综合征。这些反应包括体内和体内的反应 不同浓度的红系集落形成细胞的体外培养 促红细胞生成素。我们还使用了针对造血生长的抗体 影响不同类型心绞痛患者血清这些因子水平的因素 化疗和骨髓移植后的骨髓衰竭。 通过这些研究，我们希望了解更多关于监管的信息 影响骨髓增生性细胞表型的相互作用 人类的症状。(J)

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)