Introduction
The use of high-dose chemotherapy requires rapid hematopoietic reconstitution to avoid the problems associated with prolonged pancytopenia. This reconstitution can be achieved by either using harvested bone marrow, or by reinfusing collected hematopoietic stem cells (HSCs). Previous studies have demonstrated that human HSCs can be transduced ex vivo with retroviral vectors and then be detected in the blood or bone marrow for a considerable time following infusion. This opens up a potential therapeutic strategy of transducing HSCs with genes conferring certain important biological properties, reinfusing them into a patient after high-dose therapy, and then, following reconstitution of the hematopoietic system by these transduced cells, taking advantage of these properties. The MDR1 multidrug resistance gene confers resistance to natural-product anticancer drugs, including paclitaxel. Although tumor cells containing this gene cause problems of resistance, if normal hematopoietic cells contained this gene, then, theoretically these cells would be resistant to the effects of those anticancer drugs. If a patient's hematopoetic system was reconstituted using cells containing this gene, then there is the potential to further treat the patient with drugs such as paclitaxel without causing significant hematopoietic toxicity.