Protection of Marrow from Methotrexate Toxicity by Gene Transfer of Mutant Forms of Dihydrofolate Reductase into Hematopoietic Progenitor Cells
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.
KeywordsDihydrofolate Reductase Hematopoietic Progenitor Cell DHFR Gene Mutant DHFR Hematopoietic Stem Cell Population
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