Behavior of Feline Hematopoietic Stem Cells Years After Busulfan Exposure

• Published in: Blood Vol. 82; no. 7; pp. 2096 - 2103
• Main Authors: Abkowitz, Janis L., Linenberger, Michael L., Persik, Monica, Newton, Michael A., Guttorp, Peter
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-10-1993; The Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells; Busulfan - analogs & derivatives; Busulfan - pharmacology; Cats; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells, Cultured; Clone Cells; Female; Fundamental and applied biological sciences. Psychology; Glucosephosphate Dehydrogenase - analysis; Glucosephosphate Dehydrogenase - genetics; Hematopoiesis - drug effects; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Molecular and cellular biology; Phenotype; Probability; Stochastic Processes; Time Factors; Antineoplastic agent; Fissipedia; Carnivora; Stem cell; Hematopoietic cell; Exploration; Vertebrata; Chemotherapy; Mammalia; Treatment; Hematopoiesis; Animal; Cat
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.7.2096.2096

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.