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Behavior of feline hematopoietic stem cells years after busulfan exposure
JL Abkowitz, ML Linenberger, M Persik, MA Newton and P Guttorp
Department of Medicine, University of Washington, Seattle 98195.
The kinetics of hematopoietic stem cells were investigated in glucose-6-
phosphate dehydrogenase (G-6-PD) heterozygous cats treated with
dimethylbusulfan. Because of X-chromosome inactivation during
embryogenesis, each somatic cell from these animals contains either
maternal- or paternal-type G-6-PD. Therefore, all hematopoietic progenitor
cells carry the G-6-PD phenotype of the most primitive cell (stem cell)
from which they originate. For up to 6.5 years after dimethylbusulfan
therapy, we determined the percentages of erythroid and
granulocyte/macrophage progenitor cells with each G-6-PD phenotype.
Significant variations were seen in studies from five of six cats, showing
that the population of stem cells contributing to hematopoiesis was neither
large nor constant. With mathematical analyses, we estimated that the
proliferative potential of residual stem cells was much less than that of
normal stem cells reduced in number by autologous transplantation (Abkowitz
et al, Proc Natl Acad Sci USA 87:9062, 1990). There was no evidence for the
regeneration of a normal stem cell reserve over time; rather, damage was
most pronounced years after dimethylbusulfan exposure. These data may help
explain the high clinical incidence of aplastic anemia and myelodysplasia
after alkylating agent therapies.
Volume 82,
Issue 7,
pp. 2096-2103,
10/01/1993
Copyright © 1993 by The American Society of Hematology
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