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In summary, the ligand for c-kit has biological synergy both in vivo and in<br />

vitro with G-CSF. In vivo, the effects of G-CSF on the absolute leukocyte count<br />

and on the numbers of circulating progenitor cells are markedly enhanced by<br />

the simultaneous administration of rhSCF, but not by prior administration of<br />

rhSCF. In vitro, rhSCF enhances the proliferation of CFC and precursors of CFC<br />

that are stimulated by G-CSF. It is possible that such synergistic interactions may<br />

have clinical importance if circulation of transplantable "stem" cells also is enhanced<br />

or if stem cells in marrow are increased. Further studies to examine the<br />

in vivo synergy of rhSCF with other hematopoietic growth factors may provide<br />

novel therapeutic approaches.<br />

REFERENCES<br />

1. Zsebo KM, Wypych J, et al: Identification, purification, and biological characterization<br />

of hematopoietic stem cell factor from buffalo rat liver-conditioned medium.<br />

Cell 63:195-201,1990.<br />

2. Williams DE, Eisenman J, et al: Identification of a ligand for the c-kit proto-oncogene.<br />

Cell 63:167-174,1990.<br />

3. Huang E, Nocka K, et al: The hematopoietic growth factor KL is encoded at the SI<br />

locus and is the ligand of the c-lit receptor, the gene product of the W locus. Cell<br />

63:225-233,1990.<br />

4. Witte ON: Steel locus defines new multipotent growth factor. Cell 63:5-6,1990.<br />

5. McNiece IK, Langley KE, et al: Recombinant human stem cell factor synergizes with<br />

GM-CSF, G-CSF, IL-3, and epo to stimulate human progenitor cells of the myeloid<br />

and erythroid lineages. Exp Hematol 19:226-231,1991.<br />

6. Carow CE, Hangoc G, et al. Mast cell growth factor (c-kit ligand) supports the<br />

growth of human multipotential progenitor cells with a high replating efficiency.<br />

Blood 78:2216-2221,1991.<br />

7. Bernstein ID, Andrews RG, et al: Recombinant human stem cell factor enhances the<br />

formation of colonies by CD34+ and CD34+ lin- cells, and the generation of colonyforming<br />

cell progeny from CD34+ lin- cells cultured with IL-3, G-CSF, or GM-CSF.<br />

Blood 77:2316-2321,1991.<br />

8. Zsebo KM, Smith KA, et al: Biological characteristics of recombinant rat and human<br />

stem cell factor, in Blood Cell Growth Factors: Their Present and Future Use in<br />

Hematology and Oncology, Murphy MJ (ed), AlphaMed Press, Dayton, OH, 1991,<br />

pl94-203.<br />

9. Andrews RG, Knitter GH, et al: Recombinant human stem cell factor, a c-kit ligand,<br />

stimulates hematopoiesis in primates. Blood 78:1975-1980,1991.<br />

10. Andrews RG, Bartelmez SH, et al: A c-kit ligand, recombinant human stem cell<br />

factor, mediates reversible expansion of multiple CD34+ colony-forming cell types in<br />

blood and marrow of baboons. Blood 80:920-927,1992.<br />

11. Briddell R, Hartley C, et al: The role of stem cell factor in mobilization of peripheral<br />

blood progenitor cells (PBPC) with marrow repopulating ability in mice. Blood<br />

80(Suppl l):12a, 1992 (abstract).<br />

12. Molineux G, Migdalska A, et al: The effects on hematopoiesis of recombinant stem<br />

cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination<br />

with granulocyte colony-stimulating factor. Blood 78:961-966,1991.<br />

13. Sheridan WP, Begley G, et al: Effect of peripheral blood progenitor cells mobilized<br />

by filgrastim (G-CSF) on platelet recovery after high dose chemotherapy. Lancet<br />

339:640-644,1992.<br />

14. Molineux G, Pojda Z, et al. <strong>Transplantation</strong> potential of peripheral blood stem cells<br />

induced by granulocyte colony-stimulating factor. Blood 76:2153-2158,1990.<br />

230 SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION

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