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Clonal evolution following chemotherapy-induced stem cell depletion in cats
heterozygous for glucose-6-phosphate dehydrogenase
JL Abkowitz, RM Ott, RD Holly and JW Adamson
Department of Medicine, University of Washington, Seattle 98195.
The number of hematopoietic stem cells necessary to support normal
hematopoiesis is not known but may be small. If so, the depletion or damage
of such cells could result in apparent clonal dominance. To test this
hypothesis, dimethylbusulfan [2 to 4 mg/kg intravenously (IV) x 3] was
given to cats heterozygous for the X-linked enzyme glucose-6- phosphate
dehydrogenase (G-6-PD). These cats were the daughters of domestic X
Geoffroy parents. After the initial drug-induced cytopenias (2 to 4 weeks),
peripheral blood counts and the numbers of marrow progenitors detected in
culture remained normal, although the percentages of erythroid
burst-forming cells (BFU-E) and granulocyte/macrophage colony-forming cells
(CFU-GM) in DNA synthesis increased, as determined by the tritiated
thymidine suicide technique. In three of six cats treated, a dominance of
Geoffroy-type G-6-PD emerged among the progenitor cells, granulocytes, and
RBCs. These skewed ratios of domestic to Geoffroy-type G-6-PD have
persisted greater than 3 years. No changes in cell cycle kinetics or G-6-PD
phenotypes were noted in similar studies in six control cats. These data
suggest that clonal evolution may reflect the depletion or damage of normal
stem cells and not only the preferential growth and dominance of neoplastic
cells.
Volume 71,
Issue 6,
pp. 1687-1692,
06/01/1988
Copyright © 1988 by The American Society of Hematology
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