Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention Tumor Immunology: New Perspectives
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ly, C.
Right arrow Articles by Ong, S. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ly, C.
Right arrow Articles by Ong, S. T.
[Cancer Research 63, 5716-5722, September 15, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Bcr-Abl Kinase Modulates the Translation Regulators Ribosomal Protein S6 and 4E-BP1 in Chronic Myelogenous Leukemia Cells via the Mammalian Target of Rapamycin1

Chi Ly, Adrian F. Arechiga, Junia V. Melo, Craig M. Walsh and S. Tiong Ong2

Division of Hematology/Oncology, Department of Medicine, College of Medicine [C. L., S. T. O.], Department of Molecular Biology and Biochemistry [A. F. A., C. M. W.], and Cancer Research Institute [C. M. W., S. T. O.], University of California, Irvine, California 92697, and Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom [J. V. M.]

Identification of signaling pathways downstream of Abl tyrosine kinase may increase our understanding of the pathogenesis of chronic myelogenous leukemia (CML) and suggest strategies to improve clinical treatment of the disease. By combining the use of a phosphospecific antibody recognizing a substrate motif of serine/threonine kinases with bioinformatics, we found that the translational regulators ribosomal protein S6 and 4E-BP1 are constitutively phosphorylated in CML cells. Experiments with specific inhibitors indicated the phosphorylation is downstream of Bcr-Abl kinase and the mammalian target of rapamycin (mTOR). These results suggest that Bcr-Abl may regulate translation of critical targets in CML cells via mTOR. They also provide a rationale for testing the combination of mTOR inhibitors with the Abl kinase inhibitor imatinib in patients with CML. The mTOR inhibitor rapamycin enhanced imatinib-mediated killing of CML cell lines in vitro, and it overcame imatinib resistance in cells with Bcr-Abl gene amplification.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
E. Katsoulidis, A. Sassano, B. Majchrzak-Kita, N. Carayol, P. Yoon, A. Jordan, B. J. Druker, E. N. Fish, and L. C. Platanias
Suppression of Interferon (IFN)-inducible Genes and IFN-mediated Functional Responses in BCR-ABL-expressing Cells
J. Biol. Chem., April 18, 2008; 283(16): 10793 - 10803.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Carayol, E. Katsoulidis, A. Sassano, J. K. Altman, B. J. Druker, and L. C. Platanias
Suppression of Programmed Cell Death 4 (PDCD4) Protein Expression by BCR-ABL-regulated Engagement of the mTOR/p70 S6 Kinase Pathway
J. Biol. Chem., March 28, 2008; 283(13): 8601 - 8610.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. F. Arechiga, B. D. Bell, S. Leverrier, B. M. Weist, M. Porter, Z. Wu, Y. Kanno, S. J. Ramos, S. T. Ong, R. Siegel, et al.
A Fas-Associated Death Domain Protein/Caspase-8-Signaling Axis Promotes S-Phase Entry and Maintains S6 Kinase Activity in T Cells Responding to IL-2
J. Immunol., October 15, 2007; 179(8): 5291 - 5300.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Perrotti and P. Neviani
From mRNA Metabolism to Cancer Therapy: Chronic Myelogenous Leukemia Shows the Way
Clin. Cancer Res., March 15, 2007; 13(6): 1638 - 1642.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Yoshida, F. Yoshida, D. E. Sears, S. M. Hart, D. Ikebe, A. Muto, S. Basu, K. Igarashi, and J. V. Melo
Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1
Blood, February 1, 2007; 109(3): 1211 - 1219.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
P. Yoon, N. Giafis, J. Smith, H. Mears, E. Katsoulidis, A. Sassano, J. Altman, A. J. Redig, M. S. Tallman, and L. C. Platanias
Activation of mammalian target of rapamycin and the p70 S6 kinase by arsenic trioxide in BCR-ABL-expressing cells.
Mol. Cancer Ther., November 1, 2006; 5(11): 2815 - 2823.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
T. Ikezoe, C. Nishioka, T. Tasaka, Y. Yang, N. Komatsu, K. Togitani, H. P. Koeffler, and H. Taguchi
The antitumor effects of sunitinib (formerly SU11248) against a variety of human hematologic malignancies: enhancement of growth inhibition via inhibition of mammalian target of rapamycin signaling.
Mol. Cancer Ther., October 1, 2006; 5(10): 2522 - 2530.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Boissel, D. Rea, V. Tieng, N. Dulphy, M. Brun, J.-M. Cayuela, P. Rousselot, R. Tamouza, P. Le Bouteiller, F.-X. Mahon, et al.
BCR/ABL oncogene directly controls MHC class I chain-related molecule A expression in chronic myelogenous leukemia.
J. Immunol., April 15, 2006; 176(8): 5108 - 5116.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Notari, P. Neviani, R. Santhanam, B. W. Blaser, J.-S. Chang, A. Galietta, A. E. Willis, D. C. Roy, M. A. Caligiuri, G. Marcucci, et al.
A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation
Blood, March 15, 2006; 107(6): 2507 - 2516.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Parmar, J. Smith, A. Sassano, S. Uddin, E. Katsoulidis, B. Majchrzak, S. Kambhampati, E. A. Eklund, M. S. Tallman, E. N. Fish, et al.
Differential regulation of the p70 S6 kinase pathway by interferon {alpha} (IFN{alpha}) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells
Blood, October 1, 2005; 106(7): 2436 - 2443.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. S. Hammerman, C. J. Fox, M. J. Birnbaum, and C. B. Thompson
Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival
Blood, June 1, 2005; 105(11): 4477 - 4483.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. J. Gu, L. Santiago, and B. S. Mitchell
Synergy between imatinib and mycophenolic acid in inducing apoptosis in cell lines expressing Bcr-Abl
Blood, April 15, 2005; 105(8): 3270 - 3277.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Deininger, E. Buchdunger, and B. J. Druker
The development of imatinib as a therapeutic agent for chronic myeloid leukemia
Blood, April 1, 2005; 105(7): 2640 - 2653.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. G. Kharas and D. A. Fruman
ABL Oncogenes and Phosphoinositide 3-Kinase: Mechanism of Activation and Downstream Effectors
Cancer Res., March 15, 2005; 65(6): 2047 - 2053.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Recher, O. Beyne-Rauzy, C. Demur, G. Chicanne, C. Dos Santos, V. M.-D. Mas, D. Benzaquen, G. Laurent, F. Huguet, and B. Payrastre
Antileukemic activity of rapamycin in acute myeloid leukemia
Blood, March 15, 2005; 105(6): 2527 - 2534.
[Abstract] [Full Text] [PDF]

Home page
 ASH Education BookHome page
N. P. Shah
Loss of Response to Imatinib: Mechanisms and Management
Hematology, January 1, 2005; 2005(1): 183 - 187.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. G. Mohi, C. Boulton, T.-L. Gu, D. W. Sternberg, D. Neuberg, J. D. Griffin, D. G. Gilliland, and B. G. Neel
Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs
PNAS, March 2, 2004; 101(9): 3130 - 3135.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.