No evidence of clonal dominance in primates up to 4 years following transplantation of multidrug resistance 1 retrovirally transduced long-term repopulating cells.
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.
Bozorgmehr
Farastuk
F
Research Group Pharmacology of Cancer Treatment, German Cancer Research Center, Heidelberg, Germany.
Laufs
Stefanie
S
Sellers
Stephanie E
SE
Roeder
Ingo
I
Zeller
Walter J
WJ
Zeller
Werner J
WJ
Dunbar
Cynthia E
CE
Fruehauf
Stefan
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D002472:Cell Transformation, Viral / Q000235:genetics; D002999:Clone Cells / Q000166:cytology*; D003199:Computer Systems; D004352:Drug Resistance, Microbial / Q000235:genetics; D005500:Follow-Up Studies; D019450:Genes, MDR; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics; D006085:Graft Survival; D006251:Harvey murine sarcoma virus / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics; D019868:Kanamycin Kinase / Q000235:genetics; D008253:Macaca mulatta; D009196:Myeloproliferative Disorders / Q000209:etiology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D016133:Polymerase Chain Reaction / Q000379:methods; D011828:Radiation Chimera; D012641:Selection, Genetic; D014161:Transduction, Genetic; D016662:Virus Integration
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019868:Kanamycin Kinase