Format

Send to

Choose Destination
Mol Ther. 2014 Jan;22(1):52-8. doi: 10.1038/mt.2013.168. Epub 2013 Jul 18.

No impact of lentiviral transduction on hematopoietic stem/progenitor cell telomere length or gene expression in the rhesus macaque model.

Author information

1
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
2
Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
3
DNA Sequencing and Genomics Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
4
Molecular and Clinical Hematology Branch, National Heart, Lung and Blood Institute/National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
5
Department of Microbiology, Immunology and Molecular Genetics, David Geffen Schools of Medicine, Los Angeles, California, USA.
6
Department of Medicine, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, Wisconsin, USA.

Abstract

The occurrence of clonal perturbations and leukemia in patients transplanted with gamma-retroviral (RV) vector-transduced autologous hematopoietic stem and progenitor cells (HSPCs) has stimulated extensive investigation, demonstrating that proviral insertions may perturb adjacent proto-oncogene expression. Although enhancer-deleted lentiviruses are less likely to result in insertional oncogenesis, there is evidence that they may perturb transcript splicing, and one patient with a benign clonal expansion of lentivirally transduced HPSC has been reported. The rhesus macaque model provides an opportunity for informative long-term analysis to ask whether transduction impacts on long-term HSPC properties. We used two techniques to examine whether lentivirally transduced HSPCs from eight rhesus macaques transplanted 1-13.5 years previously are perturbed at a population level, comparing telomere length as a measure of replicative history and gene expression profile of vector positive versus vector negative cells. There were no differences in telomere lengths between sorted GFP+ and GFP- blood cells, suggesting that lentiviral (LV) transduction did not globally disrupt replicative patterns. Bone marrow GFP+ and GF- CD34+ cells showed no differences in gene expression using unsupervised and principal component analysis. These studies did not uncover any global long-term perturbation of proliferation, differentiation, or other important functional parameters of transduced HSPCs in the rhesus macaque model.

PMID:
23863881
PMCID:
PMC3978805
DOI:
10.1038/mt.2013.168
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center