SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-04-1133. This Article Full Text (PDF) All Versions of this Article: 2002-04-1133v1 100/10/3495    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 Chagraoui, H. Articles by Wendling, F. Search for Related Content PubMed PubMed Citation Articles by Chagraoui, H. Articles by Wendling, F. Social Bookmarking                   What's this? Submitted April 15, 2002 Accepted June 19, 2002 Prominent role of TGF-ß1 in thrombopoietin-induced myelofibrosis in mice Hedia Chagraoui, Emiko Komura, Micheline Tulliez, Stephane Giraudier, William Vainchenker*, and Francoise Wendling Institut Gustave Roussy PR-1, INSERM Unite 362, Villejuif, France Laboratoire d'anatomopathologie, Hopital Cochin, Paris, France * Corresponding author; email: verpre{at}igr.fr. Several studies suggest an implication of TGF-ß1 in the promotion of myelofibrosis associated with hematopoietic malignancies, but the involvement of this cytokine is not fully investigated. To test directly the impact of TGF-ß1 in the pathogenesis of myelofibrosis, bone marrow stem cells from homozygous TGF-ß1 null (TGF-ß1-/-) and wild-type (WT) littermates were infected with a retrovirus encoding the murine TPO protein and engrafted into lethally irradiated wild-type hosts for long-term reconstitution. Over the 4 months of follow-up, TPO levels in plasma were markedly elevated in both groups of mice and animals typically developed a myeloproliferative syndrome characterized by thrombocytosis, leukocytosis, splenomegaly, increased numbers of progenitors in blood and extramedullary hematopoiesis. Severe fibrosis was observed in spleen and marrow from all the mice engrafted with WT cells. In contrast, none of the mice repopulated with TGF-ß1-/- cells (chimerism > 70%) showed deposition of reticulin fibers at any time during the follow-up. In accordance with the development of fibrosis, latent TGF-ß1 levels in plasma and extracellular fluid of the spleen from mice engrafted with WT cells were increased 6-fold and 4-fold, respectively, over levels found in normal hosts, whereas no increase over baseline levels could be demonstrated in animals transplanted with TGF-ß1-/- cells. These data provide evidence that TGF-ß1 produced by hematopoietic cells is pivotal for the pathogenesis of myelofibrosis that develops in mice with TPO overexpression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-J. Lataillade, O. Pierre-Louis, H. C. Hasselbalch, G. Uzan, C. Jasmin, M.-C. Martyre, M.-C. Le Bousse-Kerdiles, and on behalf of the French INSERM and the European EU Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence Blood, October 15, 2008; 112(8): 3026 - 3035. [Abstract] [Full Text] [PDF] C. James, F. Mazurier, S. Dupont, R. Chaligne, I. Lamrissi-Garcia, M. Tulliez, E. Lippert, F.-X. Mahon, J.-M. Pasquet, G. Etienne, et al. The hematopoietic stem cell compartment of JAK2V617F-positive myeloproliferative disorders is a reflection of disease heterogeneity Blood, September 15, 2008; 112(6): 2429 - 2438. [Abstract] [Full Text] [PDF] O. Bock, J. Hoftmann, K. Theophile, K. Hussein, B. Wiese, J. Schlue, and H. Kreipe Bone Morphogenetic Proteins Are Overexpressed in the Bone Marrow of Primary Myelofibrosis and Are Apparently Induced by Fibrogenic Cytokines Am. J. Pathol., April 1, 2008; 172(4): 951 - 960. [Abstract] [Full Text] [PDF] S. O. Ciurea, D. Merchant, N. Mahmud, T. Ishii, Y. Zhao, W. Hu, E. Bruno, G. Barosi, M. Xu, and R. Hoffman Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis Blood, August 1, 2007; 110(3): 986 - 993. [Abstract] [Full Text] [PDF] M. S. Cairo Myelofibrosis with myeloid metaplasia: targeted therapy Blood, July 1, 2007; 110(1): 2 - 3. [Full Text] [PDF] O. Wagner-Ballon, D. F. Pisani, T. Gastinne, M. Tulliez, R. Chaligne, C. Lacout, F. Aurade, J.-L. Villeval, P. Gonin, W. Vainchenker, et al. Proteasome inhibitor bortezomib impairs both myelofibrosis and osteosclerosis induced by high thrombopoietin levels in mice Blood, July 1, 2007; 110(1): 345 - 353. [Abstract] [Full Text] [PDF] Y. Chang, F. Aurade, F. Larbret, Y. Zhang, J.-P. Le Couedic, L. Momeux, J. Larghero, J. Bertoglio, F. Louache, E. Cramer, et al. Proplatelet formation is regulated by the Rho/ROCK pathway Blood, May 15, 2007; 109(10): 4229 - 4236. [Abstract] [Full Text] [PDF] A. Tefferi Primary myelofibrosis and its paraneoplastic stromal effects Haematologica, May 1, 2007; 92(5): 577 - 579. [Full Text] [PDF] E. Zetterberg, A. M. Vannucchi, A. R. Migliaccio, W. Vainchenker, M. Tulliez, R. Dickie, H. Hasselbalch, R. Rogers, and J. Palmblad Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows Haematologica, May 1, 2007; 92(5): 597 - 604. [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] R. Hoffman and D. Rondelli Biology and Treatment of Primary Myelofibrosis Hematology, January 1, 2007; 2007(1): 346 - 354. [Abstract] [Full Text] [PDF] J. A. Kennedy, F. Barabe, B. J. Patterson, J. Bayani, J. A. Squire, D. L. Barber, and J. E. Dick Expression of TEL-JAK2 in primary human hematopoietic cells drives erythropoietin-independent erythropoiesis and induces myelofibrosis in vivo PNAS, November 7, 2006; 103(45): 16930 - 16935. [Abstract] [Full Text] [PDF] C. Lacout, D. F. Pisani, M. Tulliez, F. M. Gachelin, W. Vainchenker, and J.-L. Villeval JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis Blood, September 1, 2006; 108(5): 1652 - 1660. [Abstract] [Full Text] [PDF] A. Tefferi, G. Barosi, R. A. Mesa, F. Cervantes, H. J. Deeg, J. T. Reilly, S. Verstovsek, B. Dupriez, R. T. Silver, O. Odenike, et al. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT) Blood, September 1, 2006; 108(5): 1497 - 1503. [Abstract] [Full Text] [PDF] A. Tefferi, J. Cortes, S. Verstovsek, R. A. Mesa, D. Thomas, T. L. Lasho, W. J. Hogan, M. R. Litzow, J. B. Allred, D. Jones, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia Blood, August 15, 2006; 108(4): 1158 - 1164. [Abstract] [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] A. I. Schafer Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia Blood, June 1, 2006; 107(11): 4214 - 4222. [Abstract] [Full Text] [PDF] J. Staerk, C. Lacout, T. Sato, S. O. Smith, W. Vainchenker, and S. N. Constantinescu An amphipathic motif at the transmembrane-cytoplasmic junction prevents autonomous activation of the thrombopoietin receptor Blood, March 1, 2006; 107(5): 1864 - 1871. [Abstract] [Full Text] [PDF] F. Martelli, B. Ghinassi, B. Panetta, E. Alfani, V. Gatta, A. Pancrazzi, C. Bogani, A. M. Vannucchi, F. Paoletti, G. Migliaccio, et al. Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds Blood, December 15, 2005; 106(13): 4102 - 4113. [Abstract] [Full Text] [PDF] A. Tefferi Pathogenesis of Myelofibrosis With Myeloid Metaplasia J. Clin. Oncol., November 20, 2005; 23(33): 8520 - 8530. [Abstract] [Full Text] [PDF] A. M. Vannucchi, A. Pancrazzi, P. Guglielmelli, S. Di Lollo, C. Bogani, G. Baroni, L. Bianchi, A. R. Migliaccio, A. Bosi, and F. Paoletti Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic Myelofibrosis Am. J. Pathol., September 1, 2005; 167(3): 849 - 858. [Abstract] [Full Text] [PDF] A. M. Vannucchi, L. Bianchi, F. Paoletti, A. Pancrazzi, E. Torre, M. Nishikawa, M. Zingariello, A. Di Baldassarre, R. A. Rana, R. Lorenzini, et al. A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-{beta}1 in the development of myelofibrosis Blood, May 1, 2005; 105(9): 3493 - 3501. [Abstract] [Full Text] [PDF] E. Komura, C. Tonetti, V. Penard-Lacronique, H. Chagraoui, C. Lacout, J. P. LeCouedic, P. Rameau, N. Debili, W. Vainchenker, and S. Giraudier Role for the Nuclear Factor {kappa}B Pathway in Transforming Growth Factor-{beta}1 Production in Idiopathic Myelofibrosis: Possible Relationship with FK506 Binding Protein 51 Overexpression Cancer Res., April 15, 2005; 65(8): 3281 - 3289. [Abstract] [Full Text] [PDF] L. Centurione, A. Di Baldassarre, M. Zingariello, D. Bosco, V. Gatta, R. A. Rana, V. Langella, A. Di Virgilio, A. M. Vannucchi, and A. R. Migliaccio Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1low mice Blood, December 1, 2004; 104(12): 3573 - 3580. [Abstract] [Full Text] [PDF] S. Sabri, M. Jandrot-Perrus, J. Bertoglio, R. W. Farndale, V. M.-D. Mas, N. Debili, and W. Vainchenker Differential regulation of actin stress fiber assembly and proplatelet formation by {alpha}2{beta}1 integrin and GPVI in human megakaryocytes Blood, November 15, 2004; 104(10): 3117 - 3125. [Abstract] [Full Text] [PDF] S. O'Brien, A. Tefferi, and P. Valent Chronic Myelogenous Leukemia and Myeloproliferative Disease Hematology, January 1, 2004; 2004(1): 146 - 162. [Abstract] [Full Text] [PDF] H. J. Deeg, T. A. Gooley, M. E. D. Flowers, G. E. Sale, J. T. Slattery, C. Anasetti, T. R. Chauncey, K. Doney, G. E. Georges, H.-P. Kiem, et al. Allogeneic hematopoietic stem cell transplantation for myelofibrosis Blood, December 1, 2003; 102(12): 3912 - 3918. [Abstract] [Full Text] [PDF] M.-C. Martyre, V. Steunou, M.-C. LeBousse-Kerdiles, J. Wietzerbin, A. M. Vannucchi, and A. R. Migliaccio Lack of alteration in GATA-1 expression in CD34+ hematopoietic progenitors from patients with idiopathic myelofibrosis Blood, June 15, 2003; 101(12): 5087 - 5089. [Full Text] [PDF] A. Tefferi The Forgotten Myeloproliferative Disorder: Myeloid Metaplasia Oncologist, June 1, 2003; 8(3): 225 - 231. [Abstract] [Full Text] [PDF] H. Chagraoui, M. Tulliez, T. Smayra, E. Komura, S. Giraudier, T. Yun, N. Lassau, W. Vainchenker, and F. Wendling Stimulation of osteoprotegerin production is responsible for osteosclerosis in mice overexpressing TPO Blood, April 15, 2003; 101(8): 2983 - 2989. [Abstract] [Full Text] [PDF] J. L. Spivak, G. Barosi, G. Tognoni, T. Barbui, G. Finazzi, R. Marchioli, and M. Marchetti Chronic Myeloproliferative Disorders Hematology, January 1, 2003; 2003(1): 200 - 224. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020