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THE STEM CELL NICHE

No Evidence of Clonal Dominance in Primates up to 4 Years Following Transplantation of Multidrug Resistance 1 Retrovirally Transduced Long-Term Repopulating Cells

^aResearch Group Pharmacology of Cancer Treatment, German Cancer Research Center, Heidelberg, Germany;
^bDepartment of Experimental Surgery Mannheim Faculty, University of Heidelberg, and Molecular Oncology of Solid Tumors Unit, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany;
^cHematology Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA;
^dInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany;
^eDepartment of Internal Medicine V, University of Heidelberg, Heidelberg, Germany;
^fCenter for Tumor Diagnostics and Therapy, Paracelsus Klinik, Osnabrueck, Germany

Key Words. Gene therapy • Multidrug resistance 1 • CD34+ • Rhesus macaque

Correspondence: Stefan Fruehauf, M.D., Center for Tumor Diagnostics and Therapy, Paracelsus Klinik, Am Natruper Holz 69, 49076 Osnabrueck, Germany. Telephone: 49-541-9663040; Fax: 49-541-9663046; e-mail: prof.stefan.fruehauf{at}pk-mx.de

Received January 25, 2007; accepted for publication June 18, 2007.
First published online in STEM CELLS EXPRESS   July 5, 2007.



Previous murine studies have suggested that retroviral multidrug resistance 1 (MDR1) gene transfer may be associated with a myeloproliferative disorder. Analyses at a clonal level and prolonged long-term follow-up in a model with more direct relevance to human biology were lacking. In this study, we analyzed the contribution of individual CD34-selected peripheral blood progenitor cells to long-term rhesus macaque hematopoiesis after transduction with a retroviral vector either expressing the multidrug resistance 1 gene (HaMDR1 vector) or expressing the neomycin resistance (NeoR) gene (G1Na vector). We found a total of 122 contributing clones from 8 weeks up to 4 years after transplantation. One hundred two clones contained the G1Na vector, whereas only 20 clones contained the HaMDR1 vector. Here, we show for the first time real-time polymerase chain reaction based quantification of individual transduced cell clones constituting 0.0008% ± 0.0003% to 0.0041% ± 0.00032% of primate peripheral blood cells. No clonal dominance was observed.

Disclosure of potential conflicts of interest is found at the end of this article.

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