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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2771-2777
NEOPLASIA
Complement-mediated cell death induced by rituximab in B-cell
lymphoproliferative disorders is mediated in vitro by a
caspase-independent mechanism involving the generation of reactive
oxygen species
Beatriz Bellosillo,
Neus Villamor,
Armando López-Guillermo,
Silvia Marcé,
Jordi Esteve,
Elias Campo,
Dolors Colomer, and
Emili Montserrat
From the Hematopathology Unit, Department of
Hematology, Institute of Hematology and Oncology, Department of
Pathology, Postgraduate School of Hematology Farreras-Valentí;
the Institut d'Investigacions Biomèdiques August Pi i Sunyer
(IDIBAPS), Hospital Clínic; and the University of Barcelona,
Barcelona, Spain.
Mechanisms involving the in vitro effect of rituximab in cells from
55 patients with B-cell lymphoproliferative disorders were
investigated. No cytotoxic effect was observed when cells were
incubated with rituximab alone, but in the presence of human AB serum
rituximab induced complement-dependent cell death (R-CDC). A cytotoxic
effect was observed in cells from 9 of 33 patients with B-cell chronic
lymphocytic leukemia, 16 of 16 patients with mantle-cell lymphoma, 4 of
4 patients with follicular lymphoma, and 2 of 2 patients with
hairy-cell leukemia. R-CDC was observed in cells from patients
expressing more than 50 × 103 CD20 molecules per cell,
and directly correlated with the number of CD20 molecules per cell.
Preincubation with anti-CD59 increased the cytotoxic effect of
rituximab and sensitized cells from nonsensitive cases. Neither
cleavage of poly-ADP ribose polymerase (PARP) nor activation of
caspase-3 was observed in R-CDC. In addition, no cells with a
hypodiploid DNA content were detected and R-CDC was not prevented by a
broad-spectrum caspase inhibitor, suggesting a caspase-independent
mechanism. Incubation with rituximab in the presence of AB serum
induced a rapid and intense production of reactive oxygen species
(ROS). R-CDC was blocked by the incubation of cells with
N-acetyl-L-cysteine (NAC) or Tiron, 2 ROS scavengers, indicating that
the cytotoxic effect was due to the generation of superoxide
(O ) radicals. In conclusion, the results of the
present study suggest that CD20, CD59, and complement have a
role in the in vitro cytotoxic effect of rituximab, which is mediated
by a caspase-independent process that involves ROS generation.
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|
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|
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|
|
|
|
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|
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|
|
|
|
|
|
|
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105(3):
1265 - 1273.
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|
|
|
|
|
|
|
M. L. Palomba, W. K. Roberts, T. Dao, G. Manukian, J. A. Guevara-Patino, J. D. Wolchok, D. A. Scheinberg, and A. N. Houghton
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11(1):
370 - 379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. S. Lin, I. W. Flinn, R. Modali, T. A. Lehman, J. Webb, S. Waymer, M. E. Moran, M. S. Lucas, S. S. Farag, and J. C. Byrd
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105(1):
289 - 291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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10(23):
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[Full Text]
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|
|
|
|
|
|
|
G. Cartron, H. Watier, J. Golay, and P. Solal-Celigny
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104(9):
2635 - 2642.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
J. Uchida, Y. Hamaguchi, J. A. Oliver, J. V. Ravetch, J. C. Poe, K. M. Haas, and T. F. Tedder
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J. Exp. Med.,
June 21, 2004;
199(12):
1659 - 1669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Decker, M. Oelsner, R. J. Kreitman, G. Salvatore, Q.-c. Wang, I. Pastan, C. Peschel, and T. Licht
Induction of caspase-dependent programmed cell death in B-cell chronic lymphocytic leukemia by anti-CD22 immunotoxins
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103(7):
2718 - 2726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Kennedy, P. V. Beum, M. D. Solga, D. J. DiLillo, M. A. Lindorfer, C. E. Hess, J. J. Densmore, M. E. Williams, and R. P. Taylor
Rituximab Infusion Promotes Rapid Complement Depletion and Acute CD20 Loss in Chronic Lymphocytic Leukemia
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172(5):
3280 - 3288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. P. Mone, P. Huang, H. Pelicano, C. M. Cheney, J. M. Green, J. Y. Tso, A. J. Johnson, S. Jefferson, T. S. Lin, and J. C. Byrd
Hu1D10 induces apoptosis concurrent with activation of the AKT survival pathway in human chronic lymphocytic leukemia cells
Blood,
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103(5):
1846 - 1854.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Farag, I. W. Flinn, R. Modali, T. A. Lehman, D. Young, and J. C. Byrd
Fc{gamma}RIIIa and Fc{gamma}RIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia
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February 15, 2004;
103(4):
1472 - 1474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Eisenbeis, M. A. Caligiuri, and J. C. Byrd
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Clin. Cancer Res.,
December 1, 2003;
9(16):
5810 - 5812.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Di Gaetano, E. Cittera, R. Nota, A. Vecchi, V. Grieco, E. Scanziani, M. Botto, M. Introna, and J. Golay
Complement Activation Determines the Therapeutic Activity of Rituximab In Vivo
J. Immunol.,
August 1, 2003;
171(3):
1581 - 1587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Manches, G. Lui, L. Chaperot, R. Gressin, J.-P. Molens, M.-C. Jacob, J.-J. Sotto, D. Leroux, J.-C. Bensa, and J. Plumas
In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas
Blood,
February 1, 2003;
101(3):
949 - 954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Cragg, S. M. Morgan, H. T. C. Chan, B. P. Morgan, A. V. Filatov, P. W. M. Johnson, R. R. French, and M. J. Glennie
Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts
Blood,
February 1, 2003;
101(3):
1045 - 1052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Kennedy, M. D. Solga, T. A. Schuman, A. W. Chi, M. A. Lindorfer, W. M. Sutherland, P. L. Foley, and R. P. Taylor
An anti-C3b(i) mAb enhances complement activation, C3b(i) deposition, and killing of CD20+ cells by rituximab
Blood,
February 1, 2003;
101(3):
1071 - 1079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Byrd, B. L. Peterson, V. A. Morrison, K. Park, R. Jacobson, E. Hoke, J. W. Vardiman, K. Rai, C. A. Schiffer, and R. A. Larson
Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712)
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January 1, 2003;
101(1):
6 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Rose, B. E. Smith, and D. G. Maloney
Glucocorticoids and rituximab in vitro: synergistic direct antiproliferative and apoptotic effects
Blood,
August 13, 2002;
100(5):
1765 - 1773.
[Abstract]
[Full Text]
[PDF]
|
|
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B. Bellosillo, N. Villamor, A. Lopez-Guillermo, S. Marce, F. Bosch, E. Campo, E. Montserrat, and D. Colomer
Spontaneous and drug-induced apoptosis is mediated by conformational changes of Bax and Bak in B-cell chronic lymphocytic leukemia
Blood,
August 13, 2002;
100(5):
1810 - 1816.
[Abstract]
[Full Text]
[PDF]
|
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