Increased resistance and selection in paclitaxel for peripheral blood progenitor cells following transduction with the MDR1 gene Journal Article
| Authors: | Flasshove, M.; Leonard, J. P.; Bardenheuer, W.; Moore, M. A. S. |
| Article Title: | Increased resistance and selection in paclitaxel for peripheral blood progenitor cells following transduction with the MDR1 gene |
| Abstract: | Introduction: The technique of retrovirally mediated gene transfer allows the introduction and stable expression of therapeutic genes in hematopoietic cells. Clinical applications include the marking of bone marrow and peripheral blood stem cell transplants, the correction of monogenetic disorders, and the inhibition of vital infections. A specific therapeutic option for the treatment of cancer patients consists in the transfer of drug resistance genes rendering transplantable hematopoietic cells resistant to the cytotoxic drugs used in high-dose chemotherapy protocols. Methods: We have investigated the effects of MDR1 gene transfer via a retrovital vector into prestimulated CD34-enriched primary hematopoietic cells from human peripheral blood. Results: Using a PCR to detect proviral sequences within the DNA of the target cells we observed a transfer efficiency of 70% into clonogenic progenitor cells with a markedly decreasing efficiency into more immature subpopulations. Clonogenic progenitors could be rendered resistant to paclitaxel at a frequency of 14.8±2.6% when comparing MDR1 transduced cells to a mock control. Retrovirally transduced cells and mock control cells were selected in vitro for seven days in paclitaxel and then further expanded. The numbers of nucleated cells and progenitor cells were compared and revealed a twofold selective advantage for progenitors derived from MDR1- transduced cells. The proliferative capacity did not differ between MDR1- transduced and mock cells. Conclusion: Increased paclitaxel resistance and a selective advantage for in vitro-expanded hematopoietic progenitors were detected. This observation may be helpful for the design of future gene therapy trials. |
| Keywords: | nonhuman; paclitaxel; gene expression; gene transfer; genetic transduction; gene therapy; hematopoietic stem cells; hematopoietic stem cell; multidrug resistance; retrovirus; virus vector; retroviral vector; multidrug resistance protein; cancer; article |
| Journal Title: | Tumor Diagnostik und Therapie |
| Volume: | 21 |
| Issue: | 2 |
| ISSN: | 0722-219X |
| Publisher: | Georg Thieme Verlag Kg |
| Date Published: | 2000-04-01 |
| Start Page: | 51 |
| End Page: | 58 |
| Language: | English |
| DOI: | 10.1055/s-2000-8157 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
