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Science 2 March 1990:
Vol. 247. no. 4946, pp. 1079 - 1082
DOI: 10.1126/science.2408149
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Articles

Science, Vol 247, Issue 4946, 1079-1082
Copyright © 1990 by American Association for the Advancement of Science

articles

Tyrosine kinase activity and transformation potency of bcr-abl oncogene products

TG Lugo, AM Pendergast, AJ Muller, and ON Witte

Department of Microbiology, University of California, Los Angeles 90024.

Oncogenic activation of the proto-oncogene c-abl in human leukemias occurs as a result of the addition of exons from the gene bcr and truncation of the first abl exon. Analysis of tyrosine kinase activity and quantitative measurement of transformation potency in a single-step assay indicate that variation in bcr exon contribution results in a functional difference between p210bcr-abl and p185bcr-abl proteins. Thus, foreign upstream sequences are important in the deregulation of the kinase activity of the abl product, and the extent of deregulation correlates with the pathological effects of the bcr-abl proteins.


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Specific inhibition of bcr-abl gene expression by small interfering RNA.
M. Scherr, K. Battmer, T. Winkler, O. Heidenreich, A. Ganser, and M. Eder (2003)
Blood 101, 1566-1569
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A Member of Forkhead Transcription Factor FKHRL1 Is a Downstream Effector of STI571-induced Cell Cycle Arrest in BCR-ABL-expressing Cells.
N. Komatsu, T. Watanabe, M. Uchida, M. Mori, K. Kirito, S. Kikuchi, Q. Liu, T. Tauchi, K. Miyazawa, H. Endo, et al. (2003)
J. Biol. Chem. 278, 6411-6419
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BCR/ABL-mediated Increased Expression of Multiple Known and Novel Genes That May Contribute to the Pathogenesis of Chronic Myelogenous Leukemia.
S. Salesse and C. M. Verfaillie (2003)
Mol. Cancer Ther. 2, 173-182
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Interferon-alpha , but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia.
A. Burchert, S. Wolfl, M. Schmidt, C. Brendel, B. Denecke, D. Cai, L. Odyvanova, T. Lahaye, M. C. Muller, T. Berg, et al. (2003)
Blood 101, 259-264
   Abstract »    Full Text »    PDF »
New paradigms in oncological therapeutics: redefining combination chemotherapy.
D. E. Brenner (2002)
Ann. Onc. 13, 1697-1698
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A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias.
O. G. Ottmann, B. J. Druker, C. L. Sawyers, J. M. Goldman, J. Reiffers, R. T. Silver, S. Tura, T. Fischer, M. W. Deininger, C. A. Schiffer, et al. (2002)
Blood 100, 1965-1971
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The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML.
M. E. O'Dwyer, M. J. Mauro, G. Kurilik, M. Mori, S. Balleisen, S. Olson, E. Magenis, R. Capdeville, and B. J. Druker (2002)
Blood 100, 1628-1633
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Hypoxia Modifies Proliferation and Differentiation of CD34+ CML Cells.
V. Desplat, J.-L. Faucher, F. X. Mahon, P. Dello Sbarba, V. Praloran, and Z. Ivanovic (2002)
Stem Cells 20, 347-354
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Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis.
M. Nieborowska-Skorska, G. Hoser, P. Kossev, M. A. Wasik, and T. Skorski (2002)
Blood 99, 4531-4539
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Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation.
M. S. Holtz, M. L. Slovak, F. Zhang, C. L. Sawyers, S. J. Forman, and R. Bhatia (2002)
Blood 99, 3792-3800
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Approval Summary for Imatinib Mesylate Capsules in the Treatment of Chronic Myelogenous Leukemia.
M. H. Cohen, G. Williams, J. R. Johnson, J. Duan, J. Gobburu, A. Rahman, K. Benson, J. Leighton, S. K. Kim, R. Wood, et al. (2002)
Clin. Cancer Res. 8, 935-942
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Modulation of p210BCR-ABL activity in transduced primary human hematopoietic cells controls lineage programming.
Y. Chalandon, X. Jiang, G. Hazlewood, S. Loutet, E. Conneally, A. Eaves, and C. Eaves (2002)
Blood 99, 3197-3204
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The Retinoic Acid Receptor {alpha} (RAR{alpha}) Chimeric Proteins PML-, PLZF-, NPM-, and NuMA-RAR{alpha} Have Distinct Intracellular Localization Patterns.
J. L. Hummel, T. Zhang, R. A. Wells, and S. Kamel-Reid (2002)
Cell Growth Differ. 13, 173-183
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Activated STAT Signaling in Human Tumors Provides Novel Molecular Targets for Therapeutic Intervention.
R. Buettner, L. B. Mora, and R. Jove (2002)
Clin. Cancer Res. 8, 945-954
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Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis.
B. Glei{beta}ner, N. Gokbuget, C. R. Bartram, B. Janssen, H. Rieder, J. W. G. Janssen, C. Fonatsch, A. Heyll, D. Voliotis, J. Beck, et al. (2002)
Blood 99, 1536-1543
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Imatinib Mesylate -- A New Oral Targeted Therapy.
D. G. Savage and K. H. Antman (2002)
N. Engl. J. Med. 346, 683-693
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The BCR/ABL Transgene Causes Abnormal NK Cell Differentiation and Can Be Found in Circulating NK Cells of Advanced Phase Chronic Myelogenous Leukemia Patients.
H. Nakajima, R. Zhao, T. C. Lund, J. Ward, M. Dolan, B. Hirsch, and J. S. Miller (2002)
J. Immunol. 168, 643-650
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STI571: A Paradigm of New Agents for Cancer Therapeutics.
M. J. Mauro, M. O'Dwyer, M. C. Heinrich, and B. J. Druker (2002)
J. Clin. Oncol. 20, 325-334
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Pharmacologic Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase/Mitogen-activated Protein Kinase Inhibitors Interact Synergistically with STI571 to Induce Apoptosis in Bcr/Abl-expressing Human Leukemia Cells.
C. Yu, G. Krystal, L. Varticovksi, R. McKinstry, M. Rahmani, P. Dent, and S. Grant (2002)
Cancer Res. 62, 188-199
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