|
|
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.
 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:
|
|
|
|
 
F. Forconi, E. Sozzi, E. Cencini, F. Zaja, T. Intermesoli, C. Stelitano, L. Rigacci, F. Gherlinzoni, R. Cantaffa, A. Baraldi, et al.
Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior
Blood,
November 19, 2009;
114(21):
4696 - 4702.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Dornan, F. Bennett, Y. Chen, M. Dennis, D. Eaton, K. Elkins, D. French, M. A. T. Go, A. Jack, J. R. Junutula, et al.
Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma
Blood,
September 24, 2009;
114(13):
2721 - 2729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Zenz, S. Habe, T. Denzel, J. Mohr, D. Winkler, A. Buhler, A. Sarno, S. Groner, D. Mertens, R. Busch, et al.
Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial
Blood,
September 24, 2009;
114(13):
2589 - 2597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Stilgenbauer, T. Zenz, D. Winkler, A. Buhler, R. F. Schlenk, S. Groner, R. Busch, M. Hensel, U. Duhrsen, J. Finke, et al.
Subcutaneous Alemtuzumab in Fludarabine-Refractory Chronic Lymphocytic Leukemia: Clinical Results and Prognostic Marker Analyses From the CLL2H Study of the German Chronic Lymphocytic Leukemia Study Group
J. Clin. Oncol.,
August 20, 2009;
27(24):
3994 - 4001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
