Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1.
Experiments were performed to determine if retroviral-mediated transfer of the human multidrug resistance 1 gene (MDR1) into murine bone marrow cells would confer drug resistance to the cells and whether the MDR1 gene could be used as a dominant selectable marker in vivo. When mice transplanted with bone marrow cells containing a transferred MDR1 gene were treated with the cytotoxic drug taxol, a substantial enrichment for transduced bone marrow cells was observed. This demonstration of positive selection establishes the ability to amplify clones of transduced hematopoietic cells in vivo and suggests possible applications in human therapy.
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
B P
BP
Sorrentino
S J
SJ
Brandt
D
D
Bodine
M
M
Gottesman
I
I
Pastan
A
A
Cline
A W
AW
Nienhuis
D000470:Alkaloids / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001483:Base Sequence; D001853:Bone Marrow / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000502:physiology*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004351:Drug Resistance / Q000235:genetics*; D004912:Erythrocytes / Q000502:physiology; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D017239:Paclitaxel; D016133:Polymerase Chain Reaction / Q000379:methods; D011533:Proviruses / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014162:Transfection
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D009838:Oligodeoxyribonucleotides; D004247:DNA; D017239:Paclitaxel