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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by He, Y. Articles by Pear, W. S. Search for Related Content PubMed PubMed Citation Articles by He, Y. Articles by Pear, W. S. Related Collections Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2002, Vol. 99, No. 8, pp. 2957-2968 NEOPLASIA The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia-like disease by bcr/abl Yiping He, Jason A. Wertheim, Lanwei Xu, Juli P. Miller, Fredrick G. Karnell, John K. Choi, Ruibao Ren, and Warren S. Pear From the Department of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, and Department of Bioengineering, University of Pennsylvania, Philadelphia, and the Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, MA. The bcr/abl fusion in chronic myelogenous leukemia (CML) creates a chimeric tyrosine kinase with dramatically different properties than intact c-abl. In P210 bcr/abl, the bcr portion includes a coiled-coil oligomerization domain (amino acids 1-63) and a grb2-binding site at tyrosine 177 (Tyr177) that are critical for fibroblast transformation, but give variable results in other cell lines. To investigate the role of the coiled-coil domain and Tyr177 in promoting CML, 4 P210 bcr/abl-derived mutants containing different bcr domains fused to abl were constructed. All 4 mutants, (1-63) bcr/abl, (1-63) bcr/abl, Tyr177Phe bcr/abl, and (1-210) bcr/abl exhibited elevated tyrosine kinase activity and conferred factor-independent growth in cell lines. In contrast, differences in the transforming potential of the 4 mutants occurred in our mouse model, in which all mice receiving P210 bcr/abl-expressing bone marrow cells exclusively develop a myeloproliferative disease (MPD) resembling human CML. Of the 4 mutants assayed, only 1-210 bcr/abl, containing both the coiled-coil domain and Tyr177, induced MPD. Unlike full-length P210, this mutant also caused a simultaneous B-cell acute lymphocytic leukemia (ALL). The other 3 mutants, (1-63) bcr/abl, Tyr177Phe bcr/abl, and (1-63) bcr/abl, failed to induce an MPD but instead caused T-cell ALL. These results show that both the bcr coiled-coil domain and Tyr177 are required for MPD induction by bcr/abl and provide the basis for investigating downstream signaling pathways that lead to CML. © 2002 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: I. Lahortiga, C. Akin, J. Cools, T. M. Wilson, N. Mentens, D. C. Arthur, I. Maric, P. Noel, C. Kocabas, P. Marynen, et al. Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion Haematologica, January 1, 2008; 93(1): 49 - 56. [Abstract] [Full Text] [PDF] T. Kawano, M. Ito, D. Raina, Z. Wu, J. Rosenblatt, D. Avigan, R. Stone, and D. Kufe MUC1 Oncoprotein Regulates Bcr-Abl Stability and Pathogenesis in Chronic Myelogenous Leukemia Cells Cancer Res., December 15, 2007; 67(24): 11576 - 11584. [Abstract] [Full Text] [PDF] J. Chen, W.-M. Yu, H. Daino, H. E. Broxmeyer, B. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020