SELF-RENEWAL IN NORMAL/LEUKEMIC HEMOPOIETIC STEM CELLS

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Purification studies on medium conditioned by pokeweed mitogen-stimulated spleen lymphocytes (SCM) have shown that the active factor able to stimulate stem cell self-renewal is the glycoprotein Multi-CSF (IL-3). An inducible T-lymphocyte cell line (LB3) has been developed that synthesizes large amounts of Multi-CSF. The cDNA for Multi-CSF has been cloned from an mRNA library constructed from LB3 cells. The action of cloned Multi-CSF will be analyzed on the self-renewal of stem cells in three cell systems--normal marrow stem cells, Multi-CSF-dependent continuous multipotential cell lines, and v-ras-transformed hemopoietic cells. Studies will be continued on the mechanism of action of G-CSF in suppressing stem cell self-renewal in the myelomonocytic leukemia WEHI-3B, and attempts will be made to clone the receptor for G-CSF on these cells.