SEARCH:   Advanced

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 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 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 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. Related Collections Signal Transduction Hematopoiesis and Stem Cells Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS A pathobiologic 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 Alba Rana, Rodolfo Lorenzini, Elena Alfani, Giovanni Migliaccio, and Anna Rita Migliaccio From the Departments of Hematology and Experimental Pathology and Oncology, University of Florence, Florence Italy; Kirin Brewery Pharmaceutical Research Laboratory, Gunma, Japan; the Department of Biomorphology, University of Chieti, Rome, Italy; and the Quality and Safety of Animal Experimentation and the Departments of Cell Biology and Neurosciences and Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy. Idiopathic myelofibrosis (IM) is a disease characterized by marrow fibrosis, abnormal stem/progenitor cell trafficking, and extramedullary hematopoiesis frequently associated with alterations in megakaryocytes (Mks). 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 pathobiologic mechanism leading to the development of myelofibrosis in the 2 animal models is not understood. Here we show that plasma from GATA-1low mice contained normal levels of TPO. On the other hand, Mks 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, development of myelofibrosis was associated with high transforming growth factor 1 (TGF-1) content in extracellular fluids of marrow and spleen. Surprisingly, TPO treatment of GATA-1low mice restored the GATA-1 content in Mks 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 pathobiologic pathway leading to development of myelofibrosis in mice and, possibly, of IM in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Lorenzo, M. Horowitz, and Y. Choi Osteoimmunology: Interactions of the Bone and Immune System Endocr. Rev., June 1, 2008; 29(4): 403 - 440. [Abstract] [Full Text] [PDF] F. Martelli, B. Ghinassi, R. Lorenzini, A. M. Vannucchi, R. A. Rana, M. Nishikawa, S. Partamian, G. Migliaccio, and A. R. Migliaccio Thrombopoietin Inhibits Murine Mast Cell Differentiation Stem Cells, April 1, 2008; 26(4): 912 - 919. [Abstract] [Full Text] [PDF] B. S. Wilkins, W. N. Erber, D. Bareford, G. Buck, K. Wheatley, C. L. East, B. Paul, C. N. Harrison, A. R. Green, and P. J. Campbell Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes Blood, January 1, 2008; 111(1): 60 - 70. [Abstract] [Full Text] [PDF] R. Garimella, M. A. Kacena, S. E. Tague, J. Wang, M. C. Horowitz, and H. C. Anderson Expression of Bone Morphogenetic Proteins and Their Receptors in the Bone Marrow Megakaryocytes of GATA-1low Mice: A Possible Role in Osteosclerosis J. Histochem. Cytochem., July 1, 2007; 55(7): 745 - 752. [Abstract] [Full Text] [PDF] T. Nakayama, N. Mutsuga, and G. Tosato Effect of Fibroblast Growth Factor 2 on Stromal Cell-Derived Factor 1 Production by Bone Marrow Stromal Cells and Hematopoiesis J Natl Cancer Inst, February 7, 2007; 99(3): 223 - 235. [Abstract] [Full Text] [PDF] P. J. Campbell and A. R. Green The Myeloproliferative Disorders N. Engl. J. Med., December 7, 2006; 355(23): 2452 - 2466. [Full Text] [PDF] M. Dong and G. C. Blobe Role of transforming growth factor-beta in hematologic malignancies Blood, June 15, 2006; 107(12): 4589 - 4596. [Abstract] [Full Text] [PDF] O. Wagner-Ballon, H. Chagraoui, E. Prina, M. Tulliez, G. Milon, H. Raslova, J.-L. Villeval, W. Vainchenker, and S. Giraudier Monocyte/Macrophage Dysfunctions Do Not Impair the Promotion of Myelofibrosis by High Levels of Thrombopoietin. J. Immunol., June 1, 2006; 176(11): 6425 - 6433. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020