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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3322-3329. Prepublished online as a Blood First Edition Paper on August 8, 2008; DOI 10.1182/blood-2008-04-154070. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-154070v1 112/8/3322    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 Zenz, T. Articles by Stilgenbauer, S. Search for Related Content PubMed PubMed Citation Articles by Zenz, T. Articles by Stilgenbauer, S. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up Thorsten Zenz1, Alexander Kröber1, Katrin Scherer1, Sonja Häbe1, Andreas Bühler1, Axel Benner2, Tina Denzel1, Dirk Winkler1, Jennifer Edelmann1, Carsten Schwänen1, Hartmut Döhner1, and Stephan Stilgenbauer1 1 Internal Medicine III, University of Ulm; and 2 Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany The exact prognostic role of TP53 mutations (without 17p deletion) and any impact of the deletion without TP53 mutation in CLL are unclear. We studied 126 well-characterized CLL patients by direct sequencing and DHPLC to detect TP53 mutations (exons 2-11). Most patients with 17p deletions also had TP53 mutations (81%). Mutations in the absence of 17p deletions were found in 4.5%. We found a shorter survival for patients with TP53 mutation (n = 18; P = .002), which was more pronounced when analyzed from the time point of mutation detection (6.8 vs 69 months, P < .001). The survival was equally poor for patients with deletion 17p plus TP53 mutation (7.6 months, n = 13), TP53 mutation only (5.5 months, n = 5), and 17p deletion only (5.4 months, n = 3). The prognostic impact of TP53 mutation (HR 3.71) was shown to be independent of stage, VH status, and 11q and 17p deletion in multivariate analysis. Serial samples showed evidence of clonal evolution and increasing clone size during chemotherapy, suggesting that there may be patients where this treatment is potentially harmful. TP53 mutations are associated with poor sur-vival once they occur in CLL. The de-monstration of clonal evolution under selective pressure supports the biologic significance of TP53 mutations in CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Zenz, J. Mohr, E. Eldering, A. P. Kater, A. Buhler, D. Kienle, D. Winkler, J. Durig, M. H. J. van Oers, D. Mertens, et al. miR-34a as part of the resistance network in chronic lymphocytic leukemia Blood, April 16, 2009; 113(16): 3801 - 3808. [Abstract] [Full Text] [PDF]

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