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DC Dale, E Rodger, J Cebon, N Ramesh, WP Hammond and KM Zsebo
Department of Medicine, University of Washington School of Medicine,
Seattle 98195.
Grey collie dogs have cyclic fluctuations in their blood cell counts caused
by a regulatory defect of hematopoietic stem cells. To examine the role of
stem cell factor (SCF) or its receptor in this disorder, we investigated
the stimulatory effects of recombinant canine SCF (rc-SCF) on in vitro
marrow cultures, cloned and sequenced the grey collie SCF gene, and treated
three grey collies with rc-SCF, either alone or in combination with
recombinant canine granulocyte colony-stimulating factor (rcG-CSF).
Colony-forming unit granulocyte-macrophage formation from grey collie or
normal dog marrow showed similar dose-response curves for rc-SCF. Cloning
and sequencing the SCF gene for two grey collies showed no evidence of
mutations in the coding region of the SCF gene. Treatment with rc-SCF (10
to 100 micrograms/kg/d) did not induce neutrophilia except at the highest
dose (100 micrograms/kg/d), but daily rc-SCF abrogated the neutropenic
periods in doses of 20 micrograms/kg/d or greater. Combination of rc-G-CSF
(0.5 to 1.0 microgram/kg/d) with rc-SCF treatment (20 to 50
micrograms/kg/d) suggested a synergistic effect, ie, the neutrophil levels
on combined therapy were higher than the sum of the levels when these two
cytokines were given separately. Long-term treatment of these dogs with
rc-SCF in doses of 10 to 30 micrograms/kg/d was generally well tolerated,
suggesting that SCF may be useful as a therapy for some chronic
hypoproliferative disorders of hematopoiesis.
This article has been cited by other articles:
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| Copyright © 1995 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
