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Blood, 1 November 2006, Vol. 108, No. 9, pp. 2965-2971. Prepublished online as a Blood First Edition Paper on July 11, 2006; DOI 10.1182/blood-2006-03-011734. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-011734v1 108/9/2965    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rattmann, I. Articles by Moritz, T. Search for Related Content PubMed PubMed Citation Articles by Rattmann, I. Articles by Moritz, T. Related Collections Hematopoiesis and Stem Cells Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Gene transfer of cytidine deaminase protects myelopoiesis from cytidine analogs in an in vivo murine transplant model Ina Rattmann, Veronika Kleff, Ursula R. Sorg, Walter Bardenheuer, Annette Brueckner, Ralf A. Hilger, Bertram Opalka, Siegfried Seeber, Michael Flasshove, and Thomas Moritz From the Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Duisburg-Essen Medical School, Essen, Germany; and Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Hematopoietic stem cell gene transfer of the drug-resistance gene cytidine deaminase (CDD) protecting cells from the cytotoxic cytidine analogs cytarabine and gemcitabine was investigated in a murine transplant model. Following transplantation of CDD-transduced cells and cytarabine application (500 mg/kg; days 1-4; intraperitoneally) significant myeloprotection was demonstrated with nadir counts of peripheral blood granulocytes and thrombocytes of 2.9 ± 0.6/nL versus 0.7 ± 0.1/nL (P < .001) and 509 ± 147/nL versus 80 ± 9/nL (P = .008), respectively (CDD versus control). Protection also was observed from otherwise lethal gemcitabine treatment (250 mg/kg; days 1-3). Stable levels of gene-marked cells in primary and secondary recipients were demonstrated for up to 9 months, and whereas CDD overexpression clearly reduced B- and T-lymphocyte numbers, no major toxicity was observed in the myeloid compartment. Despite the profound myeloprotective properties, however, CDD overexpression did not allow for pharmacologic enrichment of transduced hematopoiesis in our model. Thus, in summary, our data establish CDD as a drug-resistance gene highly suitable for myeloprotective purposes, which, given the lack of selection observed in our hands, might best be used in combination with selectable drugresistance genes such as MGMT (P140K) or MDR1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. C. Beard, R. Sud, K. A. Keyser, C. Ironside, T. Neff, S. Gerull, G. D. Trobridge, and H.-P. Kiem Long-term polyclonal and multilineage engraftment of methylguanine methyltransferase P140K gene-modified dog hematopoietic cells in primary and secondary recipients Blood, May 21, 2009; 113(21): 5094 - 5103. [Abstract] [Full Text] [PDF] C. C. Porter and J. DeGregori Interfering RNA-mediated purine analog resistance for in vitro and in vivo cell selection Blood, December 1, 2008; 112(12): 4466 - 4474. [Abstract] [Full Text] [PDF]

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