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Sensitivity And Resistance To Therapy

Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics

Leukemia volume 16, pages 106–111 (2002)Cite this article

Abstract

In view of the recent report of a myeloproliferative syndrome in mice that had received an MDR-1-transduced haemopoietic graft, we have investigated the potential effects of MDR-1 expression on primitive haemopoietic cell growth and differentiation. Retroviral gene transfer was used to achieve exogenous expression of either MDR-1 or truncated nerve growth factor receptor (tNGFR) in the multipotent murine haemopoietic progenitor cell line, FDCP-mix. Following gene transfer, clonal lines were derived and FACS analysis confirmed appropriate expression of each transgene. MDR-1 (but not tNGFR) expression was associated with verapamil-sensitive rhodamine efflux and resistance to killing by etoposide. When growth factor responsiveness, proliferative capacity and differentiation capacity were examined, MDR-1 expressing FDCP-mix cells exhibited a normal phenotype and mimicked the response of tNGFR-expressing or untransduced FDCP-mix cells. Thus, in the model system we have used, MDR-1 does not perturb haemopoietic cell growth and development and our data do not support a myeloproliferative role for MDR-1.

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Acknowledgements

We thank Jeff Barry and Mike Hughes for FACS analysis. This work was supported by the Cancer Research Campaign, UK (CMH, DG, LJF). KGE was supported jointly by The Society for Mucopolysaccharide Disease, The Chronic Granulomatous Society and The Primary Immunodeficiency Association.

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Authors and Affiliations

  1. CRC Experimental Haematology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK

    CM Heyworth & D Gagen

  2. Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK

    D Gagen, KG Edington & LJ Fairbairn

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Heyworth, C., Gagen, D., Edington, K. et al. Retroviral transfer and expression of human MDR-1 in a murine haemopoietic stem cell line does not alter factor dependence, growth or differentiation characteristics. Leukemia 16, 106–111 (2002). https://doi.org/10.1038/sj.leu.2402333

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