No evidence of clonal dominance in primates up to 4 years following transplantation of multidrug resistance 1 retrovirally transduced long-term repopulating cells

Stem Cells. 2007 Oct;25(10):2610-8. doi: 10.1634/stemcells.2007-0017. Epub 2007 Jul 5.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Animals
  • Cell Transformation, Viral / genetics
  • Clone Cells / cytology*
  • Computer Systems
  • Drug Resistance, Microbial / genetics
  • Follow-Up Studies
  • Genes, MDR*
  • Genetic Vectors / adverse effects
  • Genetic Vectors / genetics
  • Graft Survival
  • Harvey murine sarcoma virus / genetics*
  • Hematopoiesis / genetics
  • Kanamycin Kinase / genetics
  • Macaca mulatta
  • Myeloproliferative Disorders / etiology
  • Peripheral Blood Stem Cell Transplantation / adverse effects*
  • Polymerase Chain Reaction / methods
  • Radiation Chimera
  • Selection, Genetic
  • Transduction, Genetic
  • Virus Integration

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Kanamycin Kinase