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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1116-1122. Prepublished online as a Blood First Edition Paper on May 4, 2007; DOI 10.1182/blood-2007-01-067579. This Article Full Text (PDF) Supplemental Tables Supplemental Tables and Figures All Versions of this Article: blood-2007-01-067579v1 110/4/1116    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 Knoops, L. Articles by de Jong, D. Search for Related Content PubMed PubMed Citation Articles by Knoops, L. Articles by de Jong, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 12, 2007 Accepted April 25, 2007 In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma Laurent Knoops, Rick Haas, Sanne de Kemp, Donne Majoor, Annegien Broeks, Eric Eldering, Jean Paul de Boer, Marcel Verheij, Conny van Ostrom, Annemieke de Vries, Laura van't Veer, and Daphne de Jong* Experimental Medicine and Hematology Units, Universite catholique de Louvain, Brussels, Belgium Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, Netherlands Experimental Therapy and Diagnostic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands Department of Experimental Immunology, Academic Medical Centre, Amsterdam, Netherlands Department of Hematology, The Netherlands Cancer Institute, Amsterdam, Netherlands Laboratory of Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, Bilthoven, Netherlands * Corresponding author; email: d.d.jong{at}nki.nl. Very low-dose irradiation (2 x 2 Gy) is a new, effective and safe local treatment for follicular lymphoma. To understand the biological mechanisms of this extremely effective response, we compared by microarray the gene expression profile of patient's biopsies taken before and after radiation. In all patients, a major and consistent induction of p53 target genes was seen. p53 targets involved in cell-cycle arrest and apoptosis showed the same mode of regulation , indicating that, in vivo, both are activated simultaneously. P53 upregulation, p53-mediated proliferation arrest and apoptosis were substantiated using immunohistochemistry, with activation of both the intrinsic and the extrinsic apoptotic pathways. The other induced genes revealed a whole set of biologically meaningful genes related to macrophages activation and TH1 immune response. Immunohistochemical analysis suggested a specific activation or differentiation of resident macrophages by apoptotic cells. These biological insights are important arguments to advocate the use of low dose radiotherapy as an effective palliative treatment for follicular lymphoma. Moreover, this study is the first in vivo report of the radiation-induced p53 apoptotic response in patients and suggests that this apoptotic response is not immunologically silent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. O'Shea, C. O'Riain, C. Taylor, R. Waters, E. Carlotti, F. MacDougall, J. Gribben, A. Rosenwald, G. Ott, L. M. Rimsza, et al. The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival Blood, October 15, 2008; 112(8): 3126 - 3129. [Abstract] [Full Text] [PDF]

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