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A c-kit ligand, recombinant human stem cell factor, mediates reversible
expansion of multiple CD34+ colony-forming cell types in blood and marrow
of baboons
RG Andrews, SH Bartelmez, GH Knitter, D Myerson, ID Bernstein, FR Appelbaum and KM Zsebo
Pediatric Oncology Program, Fred Hutchinson Cancer Research Center,
Seattle, WA 98104.
The ligand for the human c-kit, recombinant human stem cell factor (SCF),
was administered to baboons at doses of 200, 100, 50, 25, and 10
micrograms/kg/d. SCF induced a dose-dependent expansion of hematopoietic
colony-forming cells (CFC) of multiple types in both blood and marrow,
including colony-forming unit (CFU) granulocyte- monocyte, burst-forming
unit-erythroid, CFU-MIX, and high proliferative potential-CFC. These
changes were associated with a dose-dependent leukocytosis, involving all
leukocyte lineages, a reticulocytosis, and increases in marrow cellularity.
At 200 micrograms/kg/d of SCF, CFC in blood were increased 10-fold to
greater than 100-fold. This correlated with an increased frequency of CD34+
cells in blood. The frequency of CFC in blood approached that of marrow in
some animals. These changes were reversed within 7 to 14 days of stopping
SCF. The results of these studies suggest a role for the c-kit ligand in
stimulating the expansion of multiple CFC types in blood and marrow for
potential therapeutic purposes.
Volume 80,
Issue 4,
pp. 920-927,
08/15/1992
Copyright © 1992 by The American Society of Hematology
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