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p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with
drug resistance and is independent of MDR1/MDR3 gene expression
S el Rouby, A Thomas, D Costin, CR Rosenberg, M Potmesil, R Silber and EW Newcomb
Department of Pathology, New York University School of Medicine.
We studied 53 patients with B-cell chronic lymphocytic leukemia (B-CLL) and
found mutations of the p53 gene in 15%. Patients with p53 gene mutations
were found to have an aggressive form of B-CLL disease characterized by
advanced Rai stage, rapid lymphocyte doubling time (LDT), and resistance to
chemotherapy. While 27 of 29 treated patients (93%) without p53 mutations
achieved a partial remission, only one of seven treated patients (14%) with
p53 mutations achieved a partial remission (P = .00009). Adjusting for
prognostic factors (age, sex, race, and Rai stage), patients with p53 gene
mutations had a 13-fold greater risk of death than patients without p53
mutations (P = .013). In addition to examining the clinical relevance of
p53 gene mutations in B-CLL, we investigated the possible role of p53 gene
regulation in the expression of the multidrug resistance genes MDR1 and
MDR3. We quantitated MDR1 and MDR3 mRNA expression by reverse
transcription- polymerase chain reaction (RT-PCR). Expression of both the
MDR1 and MDR3 genes was independent of p53 gene mutation or prior drug
treatment, and did not predict for clinical response. Our findings indicate
that p53 gene mutations in B-CLL are associated with a poor clinical
outcome and may be a prognostic indicator for drug resistance.
Volume 82,
Issue 11,
pp. 3452-3459,
12/01/1993
Copyright © 1993 by The American Society of Hematology
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108(3):
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|
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107(10):
4109 - 4114.
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|
|
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|
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|
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105(5):
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|
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101(33):
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|
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|
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103(9):
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103(4):
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
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99(12):
4554 - 4561.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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August 1, 2001;
98(3):
814 - 822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-H. Lee, K. L. Rudolph, Y.-J. Ju, R. A. Greenberg, L. Cannizzaro, L. Chin, S. R. Weiler, and R. A. DePinho
Telomere dysfunction alters the chemotherapeutic profile of transformed cells
PNAS,
March 13, 2001;
98(6):
3381 - 3386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Panasci, J.-P. Paiement, G. Christodoulopoulos, A. Belenkov, A. Malapetsa, and R. Aloyz
Chlorambucil Drug Resistance in Chronic Lymphocytic Leukemia: The Emerging Role of DNA Repair
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March 1, 2001;
7(3):
454 - 461.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. R. Rai, H. Dohner, M. J. Keating, and E. Montserrat
Chronic Lymphocytic Leukemia: Case-Based Session
Hematology,
January 1, 2001;
2001(1):
140 - 156.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Dohner, S. Stilgenbauer, A. Benner, E. Leupolt, A. Krober, L. Bullinger, K. Dohner, M. Bentz, and P. Lichter
Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia
N. Engl. J. Med.,
December 28, 2000;
343(26):
1910 - 1916.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.A. SCHMITT, R.R. WALLACE-BRODEUR, C.T. ROSENTHAL, M.E. MCCURRACH, and S.W. LOWE
DNA Damage Responses and Chemosensitivity in the E{micro}-myc Mouse Lymphoma Model
Cold Spring Harb Symp Quant Biol,
January 1, 2000;
65(0):
499 - 510.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. Fan and J. R. Bertino
Modulation of Cisplatinum Cytotoxicity by p53: Effect of p53-Mediated Apoptosis and DNA Repair
Mol. Pharmacol.,
November 1, 1999;
56(5):
966 - 972.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
C. A. Schmitt, M. E. McCurrach, E. de Stanchina, R. R. Wallace-Brodeur, and S. W. Lowe
INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53
Genes & Dev.,
October 15, 1999;
13(20):
2670 - 2677.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
B. Bellosillo, N. Villamor, D. Colomer, G. Pons, E. Montserrat, and J. Gil
In Vitro Evaluation of Fludarabine in Combination With Cyclophosphamide and/or Mitoxantrone in B-Cell Chronic Lymphocytic Leukemia
Blood,
October 15, 1999;
94(8):
2836 - 2843.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Byrd, C. Shinn, R. Ravi, C. R. Willis, J. K. Waselenko, I. W. Flinn, N. A. Dawson, and M. R. Grever
Depsipeptide (FR901228): A Novel Therapeutic Agent With Selective, In Vitro Activity Against Human B-Cell Chronic Lymphocytic Leukemia Cells
Blood,
August 15, 1999;
94(4):
1401 - 1408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Wickremasinghe and A. V. Hoffbrand
Biochemical and Genetic Control of Apoptosis: Relevance to Normal Hematopoiesis and Hematological Malignancies
Blood,
June 1, 1999;
93(11):
3587 - 3600.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Byrd, C. Shinn, J. K. Waselenko, E. J. Fuchs, T. A. Lehman, P. L. Nguyen, I. W. Flinn, L. F. Diehl, E. Sausville, and M. R. Grever
Flavopiridol Induces Apoptosis in Chronic Lymphocytic Leukemia Cells Via Activation of Caspase-3 Without Evidence of bcl-2 Modulation or Dependence on Functional p53
Blood,
November 15, 1998;
92(10):
3804 - 3816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Romano, A. Lamberti, P. Tassone, F. Alfinito, S. Costantini, F. Chiurazzi, T. Defrance, P. Bonelli, F. Tuccillo, M. C. Turco, et al.
Triggering of CD40 Antigen Inhibits Fludarabine-Induced Apoptosis in B Chronic Lymphocytic Leukemia Cells
Blood,
August 1, 1998;
92(3):
990 - 995.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Cordone, S. Masi, F. R. Mauro, S. Soddu, O. Morsilli, T. Valentini, M. L. Vegna, C. Guglielmi, F. Mancini, S. Giuliacci, et al.
p53 Expression in B-Cell Chronic Lymphocytic Leukemia: A Marker of Disease Progression and Poor Prognosis
Blood,
June 1, 1998;
91(11):
4342 - 4349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. McCurrach, T. M. F. Connor, C. M. Knudson, S. J. Korsmeyer, and S. W. Lowe
bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis
PNAS,
March 18, 1997;
94(6):
2345 - 2349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Lens, P. J.J.C. De Schouwer, R. A. Hamoudi, M. Abdul-Rauf, N. Farahat, E. Matutes, T. Crook, M. J.S. Dyer, and D. Catovsky
p53 Abnormalities in B-Cell Prolymphocytic Leukemia
Blood,
March 15, 1997;
89(6):
2015 - 2023.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Rozman and E. Montserrat
Chronic Lymphocytic Leukemia
N. Engl. J. Med.,
October 19, 1995;
333(16):
1052 - 1057.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Goldsmith, J. M. Gudas, E. Schneider, and K. H. Cowan
Wild Type p53 Stimulates Expression from the Human Multidrug Resistance Promoter in a p53-negative Cell Line
J. Biol. Chem.,
January 27, 1995;
270(4):
1894 - 1898.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Lowe, S Bodis, A McClatchey, L Remington, H. Ruley, D. Fisher, D. Housman, and T Jacks
p53 status and the efficacy of cancer therapy in vivo
Science,
November 4, 1994;
266(5186):
807 - 810.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S.W. Lowe, S. Bodis, N. Bardees, A. McClatchey, L. Remington, H.E. Ruley, D.E. Fisher, T. Jacks, J. Pelletier, and D.E. Housman
Apoptosis and the Prognostic Significance of p53 Mutation
Cold Spring Harb Symp Quant Biol,
January 1, 1994;
59(0):
419 - 426.
[Abstract]
[PDF]
|
|
|
|
|
