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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0244. This Article Full Text (PDF) All Versions of this Article: 2001-12-0244v1 99/12/4568    most recent Alert me when this article is cited Alert me if a correction is posted 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 Million, R. P Articles by Van Etten, R. A Search for Related Content PubMed PubMed Citation Articles by Million, R. P Articles by Van Etten, R. A Social Bookmarking                   What's this? Submitted December 18, 2001 Accepted February 23, 2002 The Tel/Abl (ETV6/Abl) tyrosine kinase, product of complex (9;12) translocations in human leukemia, induces distinct myeloproliferative disease in mice Ryan P Million, Jon Aster, D. Gary Gilliland, and Richard A Van Etten* The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA, USA Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA HHMI and Harvard Institutes of Medicine, Harvard Medical School, Boston, MA, USA * Corresponding author; email: vanetten{at}cbr.med.harvard.edu. Several patients with clinical features of chronic myeloid leukemia (CML) have fusion of the TEL (ETV6) gene on 12p13 with ABL on 9q34 and express a chimeric Tel/Abl protein that contains the same portion of the Abl tyrosine kinase fused to Tel, an Ets family transcription factor, rather than Bcr. In a murine retroviral bone marrow transduction/transplantation model, a Tel (exon 1-5)/Abl fusion protein induced two distinct illnesses, CML-like myeloproliferative disease very similar to that induced by Bcr/Abl but with increased latency, and a novel syndrome characterized by small bowel myeloid cell infiltration and necrosis, increased circulating endotoxin and TNF-alpha, and fulminant hepatic and renal failure. Induction of both diseases required the Tel PNT homology oligomerization domain and Abl tyrosine kinase activity. Myeloid cells from mice with both diseases expressed Tel/Abl protein. Tel/Abl- and Bcr/Abl-induced CML-like disease was polyclonal and originated from cells with multilineage (myeloid/erythroid/B- and T-lymphoid) repopulating ability and the capacity to generate day 12 spleen colonies in secondary transplants, but in contrast to Bcr/Abl, neither Tel/Abl-induced disease could be adoptively transferred to irradiated secondary syngeneic recipient mice. These results demonstrate that Tel/Abl has distinct leukemogenic properties from Bcr/Abl and may act in a different bone marrow progenitor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Ko, N. Patel, T. Ikawa, H. Kawamoto, O. Frank, R. R. Rivera, R. A. Van Etten, and C. Murre Suppression of E-protein activity interferes with the development of BCR-ABL-mediated myeloproliferative disease PNAS, September 2, 2008; 105(35): 12967 - 12972. [Abstract] [Full Text] [PDF] A. Agarwal, T. G. P. Bumm, A. S. Corbin, T. O'Hare, M. Loriaux, J. VanDyke, S. G. Willis, J. Deininger, K. I. Nakayama, B. J. Druker, et al. Absence of SKP2 expression attenuates BCR-ABL-induced myeloproliferative disease Blood, September 1, 2008; 112(5): 1960 - 1970. [Abstract] [Full Text] [PDF] J. McLaughlin, D. Cheng, O. Singer, R. U. Lukacs, C. G. Radu, I. M. Verma, and O. N. 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