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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1888-1891
BRIEF REPORT
The effect of multidrug-resistance 1 gene versus neo
transduction on ex vivo and in vivo expansion of rhesus macaque
hematopoietic repopulating cells
Stephanie E. Sellers,
John
F. Tisdale,
Brian A. Agricola,
Mark E. Metzger,
Robert E. Donahue,
Cynthia E. Dunbar, and
Brian P. Sorrentino
From the Hematology Branch, the National Heart, Lung, and Blood
Institute, and the Molecular and Clinical Hematology Branch, the
National Institute of Diabetes and Digestive and Kidney Diseases, the
National Institutes of Health, Bethesda, MD, and the Biochemistry
Department, St Jude Children's Research Hospital, Memphis, TN.
Transduction of murine stem cells with a multidrug-resistance
1 gene (MDR1) retrovirus results in dramatic ex
vivo and in vivo expansion of repopulating cells accompanied by a
myeloproliferative disorder. Given the use of
MDR1-containing vectors in human trials, investigations have been extended to nonhuman primates.
Peripheral blood stem cells from 2 rhesus monkeys were collected,
CD34-enriched, split into 2 portions, and transduced with either
MDR1 vectors or neo vectors and continued in
culture for a total of 10 days before reinfusion. At engraftment, the
copy number in granulocytes was extremely high from both
MDR vectors and neo vectors, but the
copy number fell to 0.01 to 0.05 for both. There were no perturbations of the leukocyte count or differential noted. After 3 cycles of stem
cell factor/granulocyte colony-stimulating factor, there were no
changes in the levels of MDR1 vector- or neo
vector-containing cells. There was no evidence for expansion of
MDR1 vector-transduced cells. Long-term engraftment
with MDR1 vector- and neo vector-transduced cells occurred despite prolonged culture.
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