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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 Tomasson, M. H. Articles by Gilliland, D. G. Search for Related Content PubMed PubMed Citation Articles by Tomasson, M. H. Articles by Gilliland, D. G. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 5 (March 1), 1999: pp. 1707-1714 TEL/PDGFR Induces Hematologic Malignancies in Mice That Respond to a Specific Tyrosine Kinase Inhibitor Michael H. Tomasson, Ifor R. Williams, Robert Hasserjian, Chirayu Udomsakdi, Shannon M. McGrath, Juerg Schwaller, Brian Druker, and D. Gary Gilliland From the Division of Hematology, Brigham and Women's Hospital, Boston; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA; Department of Pathology, Emory University, Atlanta, GA; Hammersmith Hospital, London, UK; and Oregon Health Sciences University, Portland, OR. The TEL/PDGFR fusion protein is expressed as the consequence of a recurring t(5;12) translocation associated with chronic myelomonocytic leukemia (CMML). Unlike other activated protein tyrosine kinases associated with hematopoietic malignancies, TEL/PDGFR is invariably associated with a myeloid leukemia phenotype in humans. To test the transforming properties of TEL/PDGFR in vivo, and to analyze the basis for myeloid lineage specificity in humans, we constructed transgenic mice with TEL/PDGFR expression driven by a lymphoid-specific immunoglobulin enhancer-promoter cassette. These mice developed lymphoblastic lymphomas of both T and B lineage, demonstrating that TEL/PDGFR is a transforming protein in vivo, and that the transforming ability of this fusion is not inherently restricted to the myeloid lineage. Treatment of TEL/PDGFR transgenic animals with a protein tyrosine kinase inhibitor with in vitro activity against PDGFR (CGP57148) resulted in suppression of disease and a prolongation of survival. A therapeutic benefit was apparent both in animals treated before the development of overt clonal disease and in animals transplanted with clonal tumor cells. These results suggest that small-molecule tyrosine kinase inhibitors may be effective treatment for activated tyrosine kinase-mediated malignancies both early in the course of disease and after the development of additional transforming mutations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. H. Stover, J. Chen, B. 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