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Protection of Marrow from Methotrexate Toxicity by Gene Transfer of Mutant Forms of Dihydrofolate Reductase into Hematopoietic Progenitor Cells

  • J. R. Bertino
  • D. Banerjee
  • S. C. Zhao
  • S. Mineishi
  • E. Ercikan-Abali
  • N. Takebe
  • M. Sadelain
  • M. A. S. Moore
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)

Abstract

A potential clinical use of gene transfer technology would be to introduce via a retroviral vector, cDNAs encoding mutant forms of dihydrofolate reductase (DHFR) into hematopoietic progenitor cells, thus allowing high doses of methotrexate MTX to be safely administered. Mice bearing a chemotherapy sensitive breast cancer tumor, treated with high dose cyclophosphamide treatment and transplantated with bone marrow cells transfected with a mutant DHFR cDNA, tolerate high doses of MTX post transplant, leading to cure.

Additional studies are described that indicate that the use of a mutated nerve growth factor receptor (mNGFR) engineered into a vector also containing the S 31 mutant DHFR cDNA, allows identification of CD34+ hematopoietic progenitor cells that are expressing this surface protein.

Keywords

Dihydrofolate Reductase Hematopoietic Progenitor Cell DHFR Gene Mutant DHFR Hematopoietic Stem Cell Population 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • J. R. Bertino
  • D. Banerjee
  • S. C. Zhao
  • S. Mineishi
  • E. Ercikan-Abali
  • N. Takebe
  • M. Sadelain
  • M. A. S. Moore

There are no affiliations available

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