Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025972-06
Application #
3167122
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1983-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Walter and Eliza Hall Institute Medical Research
Department
Type
DUNS #
City
Victoria
State
Country
Australia
Zip Code
3050

  Publications

McArthur, G A; Metcalf, D; Rakar, S et al. (1995) Overexpression of C-FMS in the myeloid cell line FDC-P1 induces transformation that dissociates M-CSF-induced proliferation and differentiation. Leukemia 9:68-76
Li, C L; Johnson, G R (1995) Murine hematopoietic stem and progenitor cells: I. Enrichment and biologic characterization. Blood 85:1472-9
McArthur, G A; Longmore, G D; Klingler, K et al. (1995) Lineage-restricted recruitment of immature hematopoietic progenitor cells in response to Epo after normal hematopoietic cell transfection with EpoR. Exp Hematol 23:645-54
Li, C L; Wu, L; Antica, M et al. (1995) Purified murine long-term in vivo hematopoietic repopulating cells are not prothymocytes. Exp Hematol 23:21-5
Li, C L; Johnson, G R (1994) Stem cell factor enhances the survival but not the self-renewal of murine hematopoietic long-term repopulating cells. Blood 84:408-14
McArthur, G A; Rohrschneider, L R; Johnson, G R (1994) Induced expression of c-fms in normal hematopoietic cells shows evidence for both conservation and lineage restriction of signal transduction in response to macrophage colony-stimulating factor. Blood 83:972-81
Duhrsen, U; Novotny, J; Boyd, A W (1994) Self-renewal of a transplantable murine leukemia induced by co-culture with human stromal cell lines. Leukemia 8:490-7
Li, C L; Johnson, G R (1992) Long-term hemopoietic repopulation by Thy-1lo, Lin-, Ly6A/E+ cells. Exp Hematol 20:1309-15
Metcalf, D; Nicola, N A; Gough, N M et al. (1992) Synergistic suppression: anomalous inhibition of the proliferation of factor-dependent hemopoietic cells by combination of two colony-stimulating factors. Proc Natl Acad Sci U S A 89:2819-23
Metcalf, D (1992) Mechanisms responsible for size differences between hemopoietic colonies: an analysis using a CSF-dependent hemopoietic cell line. Int J Cell Cloning 10:116-25

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