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Transfer and expression of the human multidrug resistance gene in mouse erythroleukemia cells

E DelaFlor-Weiss, C Richardson, M Ward, A Himelstein, L Smith, S Podda, M Gottesman, I Pastan and A Bank

Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, NY 10032.

Gene therapy in humans requires the transplantation of genetically modified cells, and it is important to select only those cells capable of expressing high levels of protein from the transferred gene. Expression of the human multiple drug resistance (MDR) gene confers resistance to a variety of compounds in vitro and in vivo. To determine the feasibility of conferring recipient erythroid cells with the MDR phenotype, we have transduced mouse erythroleukemia cells (MELC) with the MDR gene in a retroviral vector. We show here that MELC clones resistant to exposure to colchicine (an MDR-responsive agent) can be isolated, and demonstrate high levels of MDR RNA and protein expression. Increasing doses of colchicine increase the level of MDR RNA and protein expression significantly. These results indicate that it is possible to transfer and express the human MDR phenotype in mouse erythroid cells by retrovirally mediated gene transfer, and that drug selection can be used to enrich or purify populations of cells containing and expressing this gene.

Volume 80, Issue 12, pp. 3106-3111, 12/15/1992
Copyright © 1992 by The American Society of Hematology


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  Copyright © 1992 by American Society of Hematology         Online ISSN: 1528-0020