title: Retroviral MDR1 gene transfer into marrow-engrafting human peripheral blood progenitor cells results in preferential transgene expression in the immature myeloid compartment rather than in mature myeloid progeny in vivo.
abstract: BACKGROUND
  The objective of multidrug resistance-1 (MDR1) gene therapy is protection of the myeloid cell lineage. It is therefore important to examine the effect of retroviral transduction on myeloid maturation. Transfer of the human MDR1 gene can confer resistance to a variety of cytostatic drugs. For a safe application in humans it is paramount to follow-up the development of transduced cells.
  
  
  METHODS
  We transduced human mobilized peripheral blood progenitor cells (PBPC) with a viral vector containing the human MDR1 cDNA and transplanted the transduced cells into non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. The progeny of the transduced cells was analyzed in detail by flow cytometry.
  
  
  RESULTS
  A detailed analysis by four-color flow cytometry showed that MDR1 transgene-expressing CD33+ myeloid cells were preferentially negative for the maturation-associated myeloid markers CD11b and CD10, while the untransduced CD33+ myeloid cells expressed significantly higher proportions of these Ag (P<0.01 each). There was no difference in the expression of B- or T-lymphoid Ag among the MDR1-transduced and untransduced lymphoid cells.
  
  
  CONCLUSIONS
  These data indicate that retroviral MDR1 gene transfer results in preferential P-glycoprotein expression in myeloid progenitor cells, which is the target cell population for myelotoxicity of cytostatic drugs.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: E C
authors.initials: EC
authors.lastname: Buss
authors.forename: S
authors.initials: S
authors.lastname: Laufs
authors.forename: S
authors.initials: S
authors.lastname: Naundorf
authors.forename: K
authors.initials: K
authors.lastname: Kuehlcke
authors.forename: K Z
authors.initials: KZ
authors.lastname: Nagy
authors.forename: W J
authors.initials: WJ
authors.lastname: Zeller
authors.forename: S
authors.initials: S
authors.lastname: Fruehauf
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002454:Cell Differentiation; D005260:Female; D005434:Flow Cytometry; D019450:Genes, MDR; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023461:Myeloid Progenitor Cells / Q000378:metabolism*; D014161:Transduction, Genetic; D019076:Transgenes; D014183:Transplantation, Heterologous
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1