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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3363-3370. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-03-0768. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0768v1 102/9/3363    most recent 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 Huettner, C. S. Articles by Tenen, D. G. Search for Related Content PubMed PubMed Citation Articles by Huettner, C. S. Articles by Tenen, D. G. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome Claudia S. Huettner, Steffen Koschmieder, Hiromi Iwasaki, Junko Iwasaki-Arai, Hanna S. Radomska, Koichi Akashi, and Daniel G. Tenen From the Harvard Institutes of Medicine, Harvard Medical School, Boston, MA; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. The BCR/ABL fusion protein is found in more than 90% of patients with chronic myeloid leukemia (CML) as well as in a subset of patients with acute B-cell leukemia. We have previously described a transgenic model for an inducible and reversible acute B-cell leukemia caused by p210 BCR/ABL. Here, we describe a new model of an inducible BCR/ABL disease by directing the expression of the oncogene to megakaryocytic progenitor cells within the murine bone marrow using the tetracycline-responsive expression system under the control of human CD34 regulatory elements. The predominant feature was the development of a chronic thrombocytosis. The condition progressed with the development of splenomegaly accompanied by lymphadenopathy in some mice. Affected animals demonstrated a dramatic increase in the number of megakaryocytes in the bone marrow and the spleen. Immunohistochemistry demonstrated that the reporter gene was expressed in hematopoietic stem cells (HSCs), common myeloid progenitor (CMP) cells, as well as in megakaryocytic/erythroid progenitor cells (MEPs). Although these mice did not display the increase in granulopoiesis commonly found in chronic myeloid leukemia (CML), the phenotype closely resembles a myeloproliferative disorder affecting the megakaryocytic lineage observed in some patients with the BCR/ABL P210 translocation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. J. Horton, V. Walf-Vorderwulbecke, S. J. Chatters, N. J. Sebire, J. de Boer, and O. Williams Acute myeloid leukemia induced by MLL-ENL is cured by oncogene ablation despite acquisition of complex genetic abnormalities Blood, May 14, 2009; 113(20): 4922 - 4929. [Abstract] [Full Text] [PDF] K. Miyazaki, N. Yamasaki, H. Oda, T. Kuwata, Y. Kanno, M. Miyazaki, Y. Komeno, J. Kitaura, Z.-i. Honda, S. Warming, et al. Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia Blood, May 7, 2009; 113(19): 4702 - 4710. [Abstract] [Full Text] [PDF] K. Kometani, M. Aoki, S. Kawamata, Y. Shinozuka, T. Era, M. Taniwaki, M. Hattori, and N. Minato Role of SPA-1 in Phenotypes of Chronic Myelogenous Leukemia Induced by BCR-ABL-Expressing Hematopoietic Progenitors in a Mouse Model. Cancer Res., October 15, 2006; 66(20): 9967 - 9976. [Abstract] [Full Text] [PDF] E. Bockamp, C. Antunes, M. Maringer, R. Heck, K. Presser, S. Beilke, S. Ohngemach, R. Alt, M. Cross, R. Sprengel, et al. Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes, and c-kit-expressing lineage-negative hematopoietic cells Blood, September 1, 2006; 108(5): 1533 - 1541. [Abstract] [Full Text] [PDF] J. R. Gothert, S. E. Gustin, M. A. Hall, A. R. Green, B. Gottgens, D. J. Izon, and C. G. Begley In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis Blood, April 1, 2005; 105(7): 2724 - 2732. [Abstract] [Full Text] [PDF] S. Koschmieder, B. Gottgens, P. Zhang, J. Iwasaki-Arai, K. Akashi, J. L. Kutok, T. Dayaram, K. Geary, A. R. Green, D. G. Tenen, et al. Inducible chronic phase of myeloid leukemia with expansion of hematopoietic stem cells in a transgenic model of BCR-ABL leukemogenesis Blood, January 1, 2005; 105(1): 324 - 334. [Abstract] [Full Text] [PDF] C. H.M. Jamieson, L. E. Ailles, S. J. Dylla, M. Muijtjens, C. Jones, J. L. Zehnder, J. Gotlib, K. Li, M. G. Manz, A. Keating, et al. Granulocyte-Macrophage Progenitors as Candidate Leukemic Stem Cells in Blast-Crisis CML N. Engl. J. Med., August 12, 2004; 351(7): 657 - 667. [Abstract] [Full Text] [PDF] B. Calabretta and D. Perrotti The biology of CML blast crisis Blood, June 1, 2004; 103(11): 4010 - 4022. 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