HEMATOPOIETIC GROWTH FACTORS, ONCOGENES, AND LEUKEMIA

造血干细胞的生长和分化依赖于

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.