1. In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma.
- Author
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Knoops L, Haas R, de Kemp S, Majoor D, Broeks A, Eldering E, de Boer JP, Verheij M, van Ostrom C, de Vries A, van't Veer L, and de Jong D
- Subjects
- Adult, Aged, Aged, 80 and over, Apoptosis radiation effects, Female, Gamma Rays, Gene Expression Profiling, Humans, Immunoenzyme Techniques, Lymphoma, B-Cell genetics, Lymphoma, B-Cell immunology, Lymphoma, B-Cell radiotherapy, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse radiotherapy, Male, Middle Aged, Mutation, Oligonucleotide Array Sequence Analysis, RNA, Messenger analysis, Gene Expression Regulation, Neoplastic physiology, Lymphoma, Follicular immunology, Lymphoma, Follicular radiotherapy, Tumor Suppressor Protein p53 genetics
- Abstract
Very low-dose irradiation (2 x 2 Gy) is a new, effective, and safe local treatment for follicular lymphoma. To understand the biologic mechanisms of this extremely effective response, we compared by microarray the gene-expression profile of patients' 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 up-regulation and 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 macrophage activation and TH1 immune response. Immunohistochemical analysis suggested a specific activation or differentiation of resident macrophages by apoptotic cells. These biologic 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.
- Published
- 2007
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