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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3493-3501. Prepublished online as a Blood First Edition Paper on January 21, 2005; DOI 10.1182/blood-2004-04-1320. This Article Full Text (PDF) All Versions of this Article: 2004-04-1320v1 105/9/3493    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 Vannucchi, A. M Articles by Migliaccio, A. R Search for Related Content PubMed PubMed Citation Articles by Vannucchi, A. M Articles by Migliaccio, A. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 7, 2004 Accepted December 26, 2004 A patho-biological pathway linking thrombopoietin, GATA-1 and TGF-1 in the development of myelofibrosis Alessandro M Vannucchi, Lucia Bianchi, Francesco Paoletti, Alessandro Pancrazzi, Eugenio Torre, Mitsuo Nishikawa, Maria Zingariello, Angela Di Baldassarre, Rosa A Rana, Rodolfo Lorenzini, Elena Alfani, Giovanni Migliaccio, and Anna R Migliaccio* Department of Hematology, University of Florence, Florence, Italy Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy Kirin Brewery Pharmaceutical Research Laboratory, Gunma, Japan Department of Biomorphology, University of Chieti, Chieti, Italy Quality and Safety of Animal Experimentation, Istituto Superiore Sanita, Rome, Italy Departments of Cell Biology and Neurosciences, Istituto Superiore Sanita, Rome, Italy Department of Biomorphology, University of Chieti, Chieti, Italy; Departments of Cell Biology and Neurosciences, Istituto Superiore Sanita, Rome, Italy Department of Biomorphology, University of Chieti, Chieti, Italy; Departments of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanita, Rome, Italy * Corresponding author; email: migliar{at}iss.it. Idiopathic myelofibrosis (IM) is a disease characterized by marrow fibrosis, abnormal stem/progenitor cell trafficking and extramedullary hemopoiesis frequently associated with alterations in megakaryocytes (Mk). Mice harboring genetic alterations in either the extrinsic (ectopic thrombopoietin expression, TPOhigh mice) or intrinsic (hypomorphic GATA-1 mutation, GATA-1low mice) control of Mk differentiation develop myelofibrosis, a syndrome similar to IM. The relationship, if any, between the patho-biological mechanism leading to the development of myelofibrosis in the two animal models is not understood. Here we show that plasma from GATA-1low mice contained normal levels of TPO. On the other hand, Mk from TPO-treated wild type animals (TPOhigh mice), as those from GATA-1low animals, had similar morphologic abnormalities and contained low GATA-1. In both animal models, the development of myelofibrosis was associated with high TGF-1 content in extracellular fluids of marrow and spleen. Surprisingly, TPO-treatment of GATA-1low mice restored the GATA-1 content in Mk and halted both defective thrombocytopoiesis and fibrosis. These data indicate that the TPOhigh and GATA-1low alterations are linked in an upstream-downstream relationship along a patho-biological pathway leading to development of myelofibrosis in mice and, possibly, of IM in men. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. I. Fortoul, A. Gonzalez-Villalva, G. Pinon-Zarate, V. Rodriguez-Lara, L. F. Montano, and L. Saldivar-Osorio Ultrastructural megakaryocyte modifications after vanadium inhalation in spleen and bone marrow J. Electron Microsc. (Tokyo), December 1, 2009; 58(6): 375 - 380. [Abstract] [Full Text] [PDF] J. Lorenzo, M. Horowitz, and Y. 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