|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 802-809
Presence of a p53 Gene Deletion in Patients With Multiple Myeloma
Predicts for Short Survival After Conventional-Dose Chemotherapy
Johannes Drach,
Jutta Ackermann,
Elke Fritz,
Elisabeth Krömer,
Rudolf Schuster,
Heinz Gisslinger,
Maria DeSantis,
Niklas Zojer,
Michael Fiegl,
Sebastian Roka,
Judith Schuster,
Renate Heinz,
Heinz Ludwig, and
Heinz Huber
From the First Department of Internal Medicine, the Division of
Clinical Oncology, and the Division of Hematology and Hemostesiology,
University of Vienna, Vienna; First Department of Internal Medicine
with Medical Oncology, Wilhelminenspital, Vienna; Ludwig
Boltzmann-Institute for Leukemia Research and Hematology, and Third
Department of Internal Medicine, Hanusch-Krankenhaus, Vienna; and
Ludwig Boltzmann-Institute for Applied Cancer Research, Kaiser Franz
Josef-Spital, Vienna, Austria.
In multiple myeloma (MM), previous studies showed that mutations of
the p53 gene are rare events in patients with newly diagnosed disease,
but it is not known whether deletions of p53 are of any significance in
MM. To address this question, we used interphase fluorescence in situ
hybridization (FISH) with a DNA probe specific for the p53 locus at
17p13 and investigated bone marrow plasma cells from 72 patients with
MM (59 patients = 81.9% before therapy). By FISH, deletions of
p53, which were found to be predominantly monoallelic, were detected in
32.8% and 54.5% of patients with newly diagnosed and relapsed MM,
respectively. Karyotypes from six of the patients with a p53 deletion
by FISH showed a structural abnormality of 17p in only one of them.
Additional FISH studies including a distal-17p probe (specific for the
D17S34 locus) provided evidence for an interstitial deletion on
17p resulting in loss of p53 hybridization signals in myeloma cells.
Among all 59 patients with newly diagnosed MM, presence of a p53
deletion was associated with stage III (P = .054), but not
with other laboratory and clinical parameters. Patients with a p53
deletion had significantly shorter survival time compared with those
without a deletion, both from the time of diagnosis (median 13.9 v 38.7 months; P < .0001) and from the time of
initiation of induction treatment consisting of conventional dose
chemotherapy (median 15.9 months v median not reached at 38 months; P < .0002). On stepwise multivariate regression
analysis, presence of a p53 deletion was the most significant independent parameter predicting for shortened survival
(P = .002). We conclude that a p53 gene deletion, which can
be identified by interphase FISH in almost a third of patients with
newly diagnosed MM, is a novel prognostic factor predicting for short
survival of MM patients treated with conventional-dose chemotherapy.
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Avet-Loiseau, C. Li, F. Magrangeas, W. Gouraud, C. Charbonnel, J.-L. Harousseau, M. Attal, G. Marit, C. Mathiot, T. Facon, et al.
Prognostic Significance of Copy-Number Alterations in Multiple Myeloma
J. Clin. Oncol.,
September 20, 2009;
27(27):
4585 - 4590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Reece, K. W. Song, T. Fu, B. Roland, H. Chang, D. E. Horsman, A. Mansoor, C. Chen, E. Masih-Khan, Y. Trieu, et al.
Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13
Blood,
July 16, 2009;
114(3):
522 - 525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Xiong, X. Wu, S. Starnes, S. K. Johnson, J. Haessler, S. Wang, L. Chen, B. Barlogie, J. D. Shaughnessy Jr, and F. Zhan
An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma
Blood,
November 15, 2008;
112(10):
4235 - 4246.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Bochtler, U. Hegenbart, F. W. Cremer, C. Heiss, A. Benner, D. Hose, M. Moos, J. Bila, C. R. Bartram, A. D. Ho, et al.
Evaluation of the cytogenetic aberration pattern in amyloid light chain amyloidosis as compared with monoclonal gammopathy of undetermined significance reveals common pathways of karyotypic instability
Blood,
May 1, 2008;
111(9):
4700 - 4705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. C. Munshi
Investigative Tools for Diagnosis and Management
Hematology,
January 1, 2008;
2008(1):
298 - 305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Jenner, P. E. Leone, B. A. Walker, F. M. Ross, D. C. Johnson, D. Gonzalez, L. Chiecchio, E. Dachs Cabanas, G. Paolo Dagrada, M. Nightingale, et al.
Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma
Blood,
November 1, 2007;
110(9):
3291 - 3300.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Wavre, A. S. Baur, M. Betz, D. Muhlematter, M. Jotterand, K. Zaman, and N. Ketterer
Case study of intracerebral plasmacytoma as an initial presentation of multiple myeloma
Neuro-oncol,
July 1, 2007;
9(3):
370 - 372.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Avet-Loiseau, M. Attal, P. Moreau, C. Charbonnel, F. Garban, C. Hulin, S. Leyvraz, M. Michallet, I. Yakoub-Agha, L. Garderet, et al.
Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome
Blood,
April 15, 2007;
109(8):
3489 - 3495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fonseca and A. K. Stewart
Targeted therapeutics for multiple myeloma: The arrival of a risk-stratified approach
Mol. Cancer Ther.,
March 1, 2007;
6(3):
802 - 810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dispenzieri, S. V. Rajkumar, M. A. Gertz, M. Q. Lacy, R. A. Kyle, P. R. Greipp, T. E. Witzig, J. A. Lust, S. J. Russell, S. R. Hayman, et al.
Treatment of Newly Diagnosed Multiple Myeloma Based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART): Consensus Statement
Mayo Clin. Proc.,
March 1, 2007;
82(3):
323 - 341.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Walker, P. E. Leone, M. W. Jenner, C. Li, D. Gonzalez, D. C. Johnson, F. M. Ross, F. E. Davies, and G. J. Morgan
Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma
Blood,
September 1, 2006;
108(5):
1733 - 1743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Stuhmer, M. Chatterjee, M. Hildebrandt, P. Herrmann, H. Gollasch, C. Gerecke, S. Theurich, L. Cigliano, R. A. Manz, P. T. Daniel, et al.
Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma
Blood,
November 15, 2005;
106(10):
3609 - 3617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Chen, B. Issa, S. Huang, E. Aston, J. Xu, M. Yu, A. R. Brothman, and M. Glenn
A Practical Approach to the Detection of Prognostically Significant Genomic Aberrations in Multiple Myeloma
J. Mol. Diagn.,
November 1, 2005;
7(5):
560 - 565.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Stewart and R. Fonseca
Prognostic and Therapeutic Significance of Myeloma Genetics and Gene Expression Profiling
J. Clin. Oncol.,
September 10, 2005;
23(26):
6339 - 6344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-Y. Huang, M. Yao, J.-L. Tang, W. Tsay, F.-Y. Lee, M.-C. Liu, C.-H. Wang, Y.-C. Chen, M.-C. Shen, and H.-F. Tien
Clinical significance of cytogenetics and interphase fluorescence in situ hybridization analysis in newly diagnosed multiple myeloma in Taiwan
Ann. Onc.,
September 1, 2005;
16(9):
1530 - 1538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Chang, C. Qi, Q.-L. Yi, D. Reece, and A. K. Stewart
p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation
Blood,
January 1, 2005;
105(1):
358 - 360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hideshima, P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson
Advances in biology of multiple myeloma: clinical applications
Blood,
August 1, 2004;
104(3):
607 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fonseca, B. Barlogie, R. Bataille, C. Bastard, P. L. Bergsagel, M. Chesi, F. E. Davies, J. Drach, P. R. Greipp, I. R. Kirsch, et al.
Genetics and Cytogenetics of Multiple Myeloma: A Workshop Report
Cancer Res.,
February 15, 2004;
64(4):
1546 - 1558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Fonseca, E. Blood, M. Rue, D. Harrington, M. M. Oken, R. A. Kyle, G. W. Dewald, B. Van Ness, S. A. Van Wier, K. J. Henderson, et al.
Clinical and biologic implications of recurrent genomic aberrations in myeloma
Blood,
June 1, 2003;
101(11):
4569 - 4575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Barille-Nion, B. Barlogie, R. Bataille, P. L. Bergsagel, J. Epstein, R. G. Fenton, J. Jacobson, W. M. Kuehl, J. Shaughnessy, and G. Tricot
Advances in Biology and Therapy of Multiple Myeloma
Hematology,
January 1, 2003;
2003(1):
248 - 278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Leroy, C. Haioun, E. Lepage, N. Le Metayer, F. Berger, E. Labouyrie, V. Meignin, B. Petit, C. Bastard, G. Salles, et al.
p53 gene mutations are associated with poor survival in low and low-intermediate risk diffuse large B-cell lymphomas
Ann. Onc.,
July 1, 2002;
13(7):
1108 - 1115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Puerto, M.J. Ramirez, R. Marcos, A. Creus, and J. Surralles
Radiation-induced chromosome aberrations in human euchromatic (17cen-p53) and heterochromatic (1cen-1q12) regions
Mutagenesis,
July 1, 2001;
16(4):
291 - 296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Gruszka-Westwood, R. A. Hamoudi, E. Matutes, E. Tuset, and D. Catovsky
p53 abnormalities in splenic lymphoma with villous lymphocytes
Blood,
June 1, 2001;
97(11):
3552 - 3558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Franke, I. Wlodarska, B. Maes, P. Vandenberghe, J. Delabie, A. Hagemeijer, and C. De Wolf-Peeters
Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances
Blood,
March 15, 2001;
97(6):
1845 - 1853.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Zojer, R. Konigsberg, J. Ackermann, E. Fritz, S. Dallinger, E. Kromer, H. Kaufmann, L. Riedl, H. Gisslinger, S. Schreiber, et al.
Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization
Blood,
March 15, 2000;
95(6):
1925 - 1930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Konigsberg, N. Zojer, J. Ackermann, E. Kromer, H. Kittler, E. Fritz, H. Kaufmann, T. Nosslinger, L. Riedl, H. Gisslinger, et al.
Predictive Role of Interphase Cytogenetics for Survival of Patients With Multiple Myeloma
J. Clin. Oncol.,
February 14, 2000;
18(4):
804 - 804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Filipits, J. Drach, G. Pohl, J. Schuster, T. Stranzl, J. Ackermann, R. Konigsberg, H. Kaufmann, H. Gisslinger, H. Huber, et al.
Expression of the Lung Resistance Protein Predicts Poor Outcome in Patients with Multiple Myeloma
Clin. Cancer Res.,
September 1, 1999;
5(9):
2426 - 2430.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
