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Optimized lentiviral transduction of erythroid precursors from healthy adults and patients with myelodysplastic syndromes

Leukemia volume 16, pages 1319–1323 (2002)Cite this article

Abstract

Lentivectors, derived from human immunodeficiency virus-1 (HIV-1), represent a novel investigational and therapeutic tool for targeting hematopoietic progenitor cells. We describe a new protocol whereby we achieved a highly efficient lentiviral transduction of erythroid precursor cells originating from the bone marrow of healthy adults and patients with myelodysplastic syndromes (MDS). CD34+ stem cells from healthy subjects were cultured with erythropoietin, IL-3 and stem cell factor, and thereby expanded approximately 300-fold. When these cultures were transduced with a lentiviral vector expressing GFP as a reporter gene, 70% glycophorin+ cells were GFP+. Although proliferation and levels of transduction were reduced in cultures of CD34+ stem cells from patients with myelodysplastic syndromes, 50% of glycophorin+ cells became GFP+, amongst which 30% were sideroblastic erythroid precursors. This study demonstrates that lentiviral vectors are capable of efficiently transducing MDS precursors and offers new perspectives to investigate the influence of specific genes on normal erythroid differentiation. This may eventually help to correct defects in patients suffering from myelodysplastic syndromes.

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Acknowledgements

We thank P Salmon and D Trono for helpful discussions and gift of reagents, L Naldini for reagents, D Wohlwend for assistance with the cell sorting and S Abraham for technical assistance. We thank JH Saurat for his support during the course of these studies. This work was supported by a grant from the Leenaards Foundation and from the Geneva Cancer League (to VP, LF and FL), by grant No. 3345-67700 (to VP) and by grant No. 32–061845 from the Swiss National Science Foundation and ‘Fondation pour la recherche hématologique (PA et AK Miescher)’ (to TM and PB).

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, University Hospital Geneva, Geneva, Switzerland

    TW Matthes, V Kindler, B Chapuis & P Beris

  2. Department of Dermatology, University Hospital Geneva, Geneva, Switzerland

    F Leuba, LE French & V Piguet

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  1. TW Matthes
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  2. V Kindler
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Matthes, T., Kindler, V., Leuba, F. et al. Optimized lentiviral transduction of erythroid precursors from healthy adults and patients with myelodysplastic syndromes. Leukemia 16, 1319–1323 (2002). https://doi.org/10.1038/sj.leu.2402527

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