The multidrug-resistance gene in gene therapy of cancer and hematopoietic disorders.
Chemoresistance genes have been identified as an impediment to anticancer drug treatment. In particular, P-glycoprotein, the product of the multidrug-resistance (MDR1) gene, plays a major role in clinical treatment failure. Conversely, expression of an MDR1 cDNA in bone marrow of transgenic animals renders hematopoietic cells chemoresistant. Efficient transfer of drug-resistance genes to normal hematopoietic progenitor cells has been achieved with the use of retroviral vectors. In this article we review approaches which use the multidrug-resistance gene to protect bone marrow from myelosuppression following chemotherapy and as a selectable markerin vivo to increase the expression of nonselectable genes which correct hereditary diseases of the hematopoietic system.
Licht
T
T
University of Ulm, Department of Internal Medicine III, Germany.
Pastan
I
I
Gottesman
M M
MM
Herrmann
F
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D015316:Genetic Therapy; D006402:Hematologic Diseases / Q000235:genetics / Q000628:therapy*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1