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

¹ Research Group Pharmacology of Cancer Treatment, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
² Clinical Cooperation Unit Molecular Oncology of Solid Tumors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
³ Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA
⁴ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstrasse 16/18, 04107 Leipzig, Germany
⁵ Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; Center for Tumor Diagnostics and Therapy, Paracelsus Klinik, Am Natruper Holz 69, 49076 Osnabrueck, Germany

^* To whom correspondence should be addressed. E-mail: prof.stefan.fruehauf{at}pk-mx.de.

	Abstract

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 (PBPCs) 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. 102 clones contained the G1Na vector, whereas only 20 clones contained the HaMDR1 vector. Here, we show for the first time real-time PCR 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.

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