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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
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Animals
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Antineoplastic Agents / pharmacology
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Calcium Channel Blockers / pharmacology
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Cell Differentiation
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Cell Division
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Clone Cells / cytology
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Clone Cells / drug effects
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Clone Cells / metabolism
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Culture Media, Conditioned / pharmacology
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Drug Resistance, Neoplasm
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Etoposide / pharmacology
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Fluorescent Dyes / metabolism
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Genes, MDR
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Hematopoietic Cell Growth Factors / pharmacology
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / metabolism*
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Humans
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Mice
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Peptide Fragments / metabolism
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism
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Recombinant Fusion Proteins / physiology
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Rhodamines / metabolism
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Transfection
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Verapamil / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antineoplastic Agents
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Calcium Channel Blockers
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Culture Media, Conditioned
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Fluorescent Dyes
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Hematopoietic Cell Growth Factors
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Peptide Fragments
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Receptors, Nerve Growth Factor
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Recombinant Fusion Proteins
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Rhodamines
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Etoposide
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Verapamil