PMID: 11920652Mar 29, 2002Paper

Genetic protection of repopulating hematopoietic cells with an improved MDR1-retrovirus allows administration of intensified chemotherapy following stem cell transplantation in mice

International Journal of Cancer. Journal International Du Cancer
Alexander CarpinteiroS Hegewisch-Becker

Abstract

This study was undertaken to analyze the hematotoxicity of paclitaxel (Taxol) and to test whether transduction of repopulating hematopoietic cells with a retroviral vector (SF1m) expressing the human multidrug resistance 1 gene (MDR1) would permit dose intensification following bone marrow transplantation (BMT). While the regimen chosen (8 x 20 mg/kg i.p. within 12 days) produced a non-lethal, reversible hematotoxicity in mice with steady-state hematopoiesis, only 35.3% (6/17) of control mice survived when treated starting 14 days post BMT. In contrast, 83.3% (15/18) of mice transplanted with SF1m-transduced cells survived, owing to a significant protection against severe acute myelotoxicity (as determined by neutrophil counts, white and red blood cell counts and values for hemoglobin and hematocrit). After recovery from chemotherapy, an increase of myeloid cells that were resistant to colchicine and effluxed the fluorochrome Rhodamine 123 was observed in SF1m-mice, but not in controls. These results reveal that the lethal, dose-limiting hematotoxicity of an intensified post-transplantation chemotherapy with paclitaxel can be prevented by retroviral transfer of the MDR1 gene to a minor proportion of repopulating cells. Our mous...Continue Reading

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Citations

Oct 22, 2003·Experimental Cell Research·Emma K Baker, Assam El-Osta
Sep 6, 2003·Archives of Medical Research·Kevin R Smith
May 6, 2003·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·S LaufsS Fruehauf
Jan 5, 2010·Journal of Experimental & Clinical Cancer Research : CR·ZhenZhen ZhaoXianQing Jin
Dec 15, 2015·Journal of Experimental & Clinical Cancer Research : CR·Sebastian BrennigThomas Moritz
Dec 30, 2003·Journal of Surgical Oncology·Rhiannon M Hughes
Apr 20, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Janis L AbkowitzPeter Guttorp
Oct 14, 2014·World Journal of Gastroenterology : WJG·Si-Xue LiuYing-Qiang Zhong
Jan 4, 2003·Blood·Christopher BaumChristof von Kalle

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