HEMATOPOIETIC GROWTH FACTORS, ONCOGENES, AND LEUKEMIA

造血干细胞的生长和分化依赖于 被称为造血生长因子的分泌蛋白的活性1，2。一 白血病发生研究的核心问题之一是 这些生长因子在白血病细胞中发生了改变。最近有两 人多能生长因子、人GM-CSF 1和IL-3已被 分子克隆使得蛋白质产物易于纯化， 同质性这两个因素都支持了 红系和髓系的多种造血干细胞 血统1，2.另一方面，白血病细胞增殖反应 生长因子与分化分离（67）。我们最近 显示癌基因c-myb组成型表达阻止DMSO Friend小鼠红白血病（FMEL）细胞的诱导分化。在 此外，c-myb还被认为是造血干细胞的有丝分裂原。 祖细胞（7）。我们将分析c-myb是否参与了有丝分裂过程， 对IL-3和GM-CSF的应答。正常的造血祖细胞 用c-myb转染，看看这是否会解离生长因子诱导的 从分化中成长。此外，参与有丝分裂的基因 将鉴定对GM-CSF和IL-3的应答。 因为荷尔蒙 与受体相互作用是我们理解GM-CSF的关键， IL-3对细胞的作用，构建了一个独特的cDNA克隆载体， 分子克隆各自的受体。这是一个理想的系统研究 参与生长因子刺激的分子事件，和 这些事件在白血病细胞中是如何改变的。

The growth and differentiation of hematopoietic stem cells dependent on the activities of secreted proteins termed hematopoietic growth factors 1,2. One of the central issues in the study of leukemogenesis is how the interactions of theses growth factors is altered in the leukemic cell. Recently, two human pluripotent growth factors, human GM-CSF1 and IL-3 have been molecularly cloned enabling the protein product to be easily purified to homogeneity. Both of these factors support the growth and differentiation of a wide variety of hematopoietic stem cells of both erythroid and myeloid lineages 1,2. On the other hand, leukemic cell proliferation in response to growth factors is dissociated from differentiation (67). We have recently shown that constitutive expression of the oncogene c-myb prevents DMSO induced differentiation of Friend Mouse Erythroleukemia (FMEL) cells. In addition, c-myb has been implicated as a mitogen for hematopoietic progenitors (7). We will analyze whether c-myb is involved in the mitogenic response to IL-3 and GM-CSF. Normal hematopoietic progenitors will be transfected with a c-myb to see if this dissociates growth factor induced growth from differentiation. In addition, genes involved in the mitogenic response to GM-CSF and IL-3 will be identified. Since the hormone interactions with receptor are essential in our understanding of GM-CSF and IL-3 effects on cells, a unique cDNA cloning vector has been constructed to molecularly clone the respective receptors. This is an ideal system to study the molecular events which are involved in growth factor stimulation, and how these events are altered in a leukemic cell.