|
|
 Previous Article | Table of Contents | Next Article 
Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-
chloro-2'-deoxyadenosine and 9-beta-D-arabinosyl-2-fluoroadenine
LE Robertson, S Chubb, RE Meyn, M Story, R Ford, WN Hittelman and W Plunkett
Department of Hematology, University of Texas, M.D. Anderson Cancer Center,
Houston 77030.
2-Chloro-2'-deoxyadenosine (CldAdo) and 9-beta-D-arabinosyl-2-
fluoroadenine (F-ara-A) have shown marked activity in the treatment of
indolent lymphoid malignancies. Based on the susceptibility of various
lymphocyte populations to apoptosis, we investigated whether CldAdo or
F-ara-A would induce this process in lymphocytes from patients with chronic
lymphocytic leukemia (CLL). In vitro exposure of leukemic lymphocytes to
CldAdo or F-ara-A for 24 to 72 hours elicited features of apoptosis visible
by light and electron microscopy. Analysis of DNA integrity showed DNA
cleavage into nucleosomal-sized multimers. Using a quantitative assay,
drug-induced DNA fragmentation was both time and dose dependent. Inhibition
of active macromolecular synthesis did not prevent drug-induced
fragmentation; however, both drug-induced and spontaneous DNA fragmentation
were prevented by intracellular calcium chelation. In vitro culture with
phorbol ester generally decreased drug- induced DNA cleavage. After
prolonged incubation, CLL cells exhibited spontaneous cleavage; albeit, at
significantly lower rates than drug- treated cells. Heterogeneity was
observed for spontaneous and drug- induced DNA fragmentation and was
significantly lower in B-leukemic cells obtained from patients with
high-risk and refractory disease. We conclude that CldAdo and F-ara-A are
potent inducers of apoptotic death in CLL and that this feature correlates
with the disease status.
Volume 81,
Issue 1,
pp. 143-150,
01/01/1993
Copyright © 1993 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:
|
|
|
|
 
D. Trachootham, H. Zhang, W. Zhang, L. Feng, M. Du, Y. Zhou, Z. Chen, H. Pelicano, W. Plunkett, W. G. Wierda, et al.
Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism
Blood,
September 1, 2008;
112(5):
1912 - 1922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kojima, M. Konopleva, T. McQueen, S. O'Brien, W. Plunkett, and M. Andreeff
Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia
Blood,
August 1, 2006;
108(3):
993 - 1000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. King, V. L. Damaraju, M. F. Vickers, S. Y. Yao, T. Lang, T. E. Tackaberry, D. A. Mowles, A. M. L. Ng, J. D. Young, and C. E. Cass
A Comparison of the Transportability, and Its Role in Cytotoxicity, of Clofarabine, Cladribine, and Fludarabine by Recombinant Human Nucleoside Transporters Produced in Three Model Expression Systems
Mol. Pharmacol.,
January 1, 2006;
69(1):
346 - 353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. B. Parekh and J. W. Putney Jr.
Store-Operated Calcium Channels
Physiol Rev,
April 1, 2005;
85(2):
757 - 810.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rosenwald, E. Y. Chuang, R. E. Davis, A. Wiestner, A. A. Alizadeh, D. C. Arthur, J. B. Mitchell, G. E. Marti, D. H. Fowler, W. H. Wilson, et al.
Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response
Blood,
September 1, 2004;
104(5):
1428 - 1434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Pelicano, L. Feng, Y. Zhou, J. S. Carew, E. O. Hileman, W. Plunkett, M. J. Keating, and P. Huang
Inhibition of Mitochondrial Respiration: A NOVEL STRATEGY TO ENHANCE DRUG-INDUCED APOPTOSIS IN HUMAN LEUKEMIA CELLS BY A REACTIVE OXYGEN SPECIES-MEDIATED MECHANISM
J. Biol. Chem.,
September 26, 2003;
278(39):
37832 - 37839.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhou, E. O. Hileman, W. Plunkett, M. J. Keating, and P. Huang
Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents
Blood,
May 15, 2003;
101(10):
4098 - 4104.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Campas, J. M. Lopez, A. F. Santidrian, M. Barragan, B. Bellosillo, D. Colomer, and J. Gil
Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes
Blood,
May 1, 2003;
101(9):
3674 - 3680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Molina-Arcas, B. Bellosillo, F. J. Casado, E. Montserrat, J. Gil, D. Colomer, and M. Pastor-Anglada
Fludarabine uptake mechanisms in B-cell chronic lymphocytic leukemia
Blood,
March 15, 2003;
101(6):
2328 - 2334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Itoh, T. Kitano, M. Watanabe, T. Kondo, T. Yabu, Y. Taguchi, K. Iwai, M. Tashima, T. Uchiyama, and T. Okazaki
Possible Role of Ceramide as an Indicator of Chemoresistance: Decrease of the Ceramide Content via Activation of Glucosylceramide Synthase and Sphingomyelin Synthase in Chemoresistant Leukemia
Clin. Cancer Res.,
January 1, 2003;
9(1):
415 - 423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sarfati, V. Mateo, S. Baudet, M. Rubio, C. Fernandez, F. Davi, J.-L. Binet, J. Delic, and H. Merle-Beral
Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells
Blood,
January 1, 2003;
101(1):
265 - 269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
M. Barragan, B. Bellosillo, C. Campas, D. Colomer, G. Pons, and J. Gil
Involvement of protein kinase C and phosphatidylinositol 3-kinase pathways in the survival of B-cell chronic lymphocytic leukemia cells
Blood,
April 15, 2002;
99(8):
2969 - 2976.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. de la Fuente, B. Casanova, J. V. Moyano, M. Garcia-Gila, L. Sanz, J. Garcia-Marco, A. Silva, and A. Garcia-Pardo
Engagement of {alpha}4{beta}1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine
J. Leukoc. Biol.,
March 1, 2002;
71(3):
495 - 502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chandra, E. Mansson, V. Gogvadze, S. H. Kaufmann, F. Albertioni, and S. Orrenius
Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c release
Blood,
January 15, 2002;
99(2):
655 - 663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yamauchi, B. J. Nowak, M. J. Keating, and W. Plunkett
DNA Repair Initiated in Chronic Lymphocytic Leukemia Lymphocytes by 4-Hydroperoxycyclophosphamide Is Inhibited by Fludarabine and Clofarabine
Clin. Cancer Res.,
November 1, 2001;
7(11):
3580 - 3589.
[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
Clin. Cancer Res.,
March 1, 2001;
7(3):
454 - 461.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Harvey, R. Decker, Y. Dai, G. Schaefer, L. Tang, L. Kramer, P. Dent, and S. Grant
Interactions between 2-Fluoroadenine 9-{beta}-D-Arabinofuranoside and the Kinase Inhibitor UCN-01 in Human Leukemia and Lymphoma Cells
Clin. Cancer Res.,
February 1, 2001;
7(2):
320 - 330.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Fettucciari, E. Rosati, L. Scaringi, P. Cornacchione, G. Migliorati, R. Sabatini, I. Fetriconi, R. Rossi, and P. Marconi
Group B Streptococcus Induces Apoptosis in Macrophages
J. Immunol.,
October 1, 2000;
165(7):
3923 - 3933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Pettitt, P. D. Sherrington, and J. C. Cawley
Role of Poly(ADP-ribosyl)ation in the Killing of Chronic Lymphocytic Leukemia Cells by Purine Analogues
Cancer Res.,
August 1, 2000;
60(15):
4187 - 4193.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. Genini, I. Budihardjo, W. Plunkett, X. Wang, C. J. Carrera, H. B. Cottam, D. A. Carson, and L. M. Leoni
Nucleotide Requirements for the in Vitro Activation of the Apoptosis Protein-activating Factor-1-mediated Caspase Pathway
J. Biol. Chem.,
January 7, 2000;
275(1):
29 - 34.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chandra, I. Niemer, J. Gilbreath, K.-O. Kliche, M. Andreeff, E. J. Freireich, M. Keating, and D. J. McConkey
Proteasome Inhibitors Induce Apoptosis in Glucocorticoid-Resistant Chronic Lymphocytic Leukemic Lymphocytes
Blood,
December 1, 1998;
92(11):
4220 - 4229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Bellosillo, M. Pique, M. Barragan, E. Castano, N. Villamor, D. Colomer, E. Montserrat, G. Pons, and J. Gil
Aspirin and Salicylate Induce Apoptosis and Activation of Caspases in B-Cell Chronic Lymphocytic Leukemia Cells
Blood,
August 15, 1998;
92(4):
1406 - 1414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Leoni, Q. Chao, H. B. Cottam, D. Genini, M. Rosenbach, C. J. Carrera, I. Budihardjo, X. Wang, and D. A. Carson
Induction of an apoptotic program in cell-free extracts by 2-chloro-2'-deoxyadenosine 5'-triphosphate and cytochrome c
PNAS,
August 4, 1998;
95(16):
9567 - 9571.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kitada, J. Andersen, S. Akar, J. M. Zapata, S. Takayama, S. Krajewski, H.-G. Wang, X. Zhang, F. Bullrich, C. M. Croce, et al.
Expression of Apoptosis-Regulating Proteins in Chronic Lymphocytic Leukemia: Correlations With In Vitro and In Vivo Chemoresponses
Blood,
May 1, 1998;
91(9):
3379 - 3389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chandra, J. Gilbreath, E. J Freireich, K.-O. Kliche, M. Andreeff, M. Keating, and D. J. McConkey
Protease Activation Is Required for Glucocorticoid-Induced Apoptosis in Chronic Lymphocytic Leukemic Lymphocytes
Blood,
November 1, 1997;
90(9):
3673 - 3681.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Konig, L. Wrazel, R. P. Warrell Jr, R. Rivi, P. P. Pandolfi, A. Jakubowski, and J. L. Gabrilove
Comparative Activity of Melarsoprol and Arsenic Trioxide in Chronic B-Cell Leukemia Lines
Blood,
July 15, 1997;
90(2):
562 - 570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K Morris, J. M Kolesar, and J. G Kuhn
Review : Purine nucleoside analogs: fludarabine, entostatin and cladribine: Part 3: cladribine
Journal of Oncology Pharmacy Practice,
June 1, 1997;
3(2):
94 - 109.
[PDF]
|
|
|
|
|
|
|
B. Bellosillo, M. Dalmau, D. Colomer, and J. Gil
Involvement of CED-3/ICE Proteases in the Apoptosis of B-Chronic Lymphocytic Leukemia Cells
Blood,
May 1, 1997;
89(9):
3378 - 3384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Hentosh and M. Tibudan
2-Chloro-2'-deoxyadenosine, an Antileukemic Drug, Has an Early Effect on Cellular Mitochondrial Function
Mol. Pharmacol.,
April 1, 1997;
51(4):
613 - 619.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Hortelano and L. Bosca
6-Mercaptopurine Decreases the Bcl-2/Bax Ratio and Induces Apoptosis in Activated Splenic B Lymphocytes
Mol. Pharmacol.,
March 1, 1997;
51(3):
414 - 421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-i. Kamiya, P. Huang, and W. Plunkett
Inhibition of the 3' right-arrow 5' Exonuclease of Human DNA Polymerase epsilon by Fludarabine-terminated DNA
J. Biol. Chem.,
August 9, 1996;
271(32):
19428 - 19435.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Fidias, B. A. Chabner, and M. L. Grossbard
Purine Analogs for the Treatment of Low-Grade Lymphoproliferative Disorders
Oncologist,
June 1, 1996;
1(3):
125 - 139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J McConkey
At least two ways to apoptose: The 2-chlorodeoxyadenosine-induced cell death signalling pathway in human thymocytes is different from that induced by 2-chloroadenosine Szondy Z Biochemical Journal, 1995; 311: 585 - 588
Human and Experimental Toxicology,
March 1, 1996;
15(3):
274 - 276.
[PDF]
|
|
|
|
|
|
|
A. Saven and L. Piro
Newer Purine Analogues for the Treatment of Hairy-Cell Leukemia
N. Engl. J. Med.,
March 10, 1994;
330(10):
691 - 697.
[Full Text]
|
|
|
|
|
|
|
S. O'Brien, H. Kantarjian, E. Estey, C. Koller, B. Robertson, M. Beran, M. Andreeff, S. Pierce, and M. Keating
Lack of Effect of 2-Chlorodeoxyadenosine Therapy in Patients with Chronic Lymphocytic Leukemia Refractory to Fludarabine Therapy
N. Engl. J. Med.,
February 3, 1994;
330(5):
319 - 322.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. B. Miller and D. P. Schenkein
Hematology
JAMA,
July 14, 1993;
270(2):
216 - 217.
[Abstract]
[PDF]
|
|
|
|
|
