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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2278-2286. Prepublished online as a Blood First Edition Paper on June 19, 2008; DOI 10.1182/blood-2007-12-128751. This Article Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2007-12-128751v1 112/6/2278    most recent Alert me when this article is cited Alert me if a correction is posted 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 Newrzela, S. Articles by von Laer, D. Search for Related Content PubMed PubMed Citation Articles by Newrzela, S. Articles by von Laer, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 17, 2007 Accepted May 12, 2008 Resistance of mature T cells to oncogene transformation Sebastian Newrzela, Kerstin Cornils, Zhixiong Li, Christopher Baum, Martijn H. Brugman, Marianne Hartmann, Johann Meyer, Sylvia Hartmann, Martin-Leo Hansmann, Boris Fehse, and Dorothee von Laer* Applied Virology and Gene Therapy, Georg-Speyer-Haus, Frankfurt am Main, Hessen, Germany Experimental Pediatric Oncology and Hematology, University Hospital of the Johann Wolfgang Goethe-University, Frankfurt am Main, Hessen, Germany Department of Experimental Hematology, Hannover Medical School, Hannover, Niedersachsen, Germany Department of Pathology, University of Frankfurt, Frankfurt am Main, Hessen, Germany * Corresponding author; email: laer{at}em.uni-frankfurt.de. Leukemia caused by retroviral insertional mutagenesis after stem-cell gene transfer has been reported in several experimental animals and in patients treated for X-linked SCID. Here, we analyzed whether gene transfer into mature T cells bears the same genotoxic risk. To address this issue in an experimental 'worst case scenario', we transduced mature T cells and hematopoietic progenitor cells from C57BL/6 (Ly5.1) donor mice with high copy numbers of gammaretroviral vectors encoding the potent T cell oncogenes LMO2, TCL1 or TrkA, a constitutively active mutant of TrkA. After transplantation into RAG-1 deficient recipients (Ly5.2), stem cell transplanted animals developed T cell lymphoma/leukemia for all investigated oncogenes with a characteristic phenotype and after characteristic latency periods. Ligation-mediated PCR analysis revealed mono- or oligoclonality of the malignancies. In striking contrast, none of the mice transplanted with T cells transduced with the same vectors developed leukemia/lymphoma despite persistence of gene-modified cells. Thus our data provide direct evidence that mature T cells are less prone to transformation than hematopoietic progenitor cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Leukemia takes center (late) stage Utpal P. Davé Blood 2008 112: 2175-2176. [Full Text] [PDF] This article has been cited by other articles: D. von Laer Peaceful coexistence or clonal dominance? Blood, October 22, 2009; 114(17): 3507 - 3508. [Full Text] [PDF]

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