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Blood, 1 August 2007, Vol. 110, No. 3, pp. 986-993. Prepublished online as a Blood First Edition Paper on May 1, 2007; DOI 10.1182/blood-2006-12-064626. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2006-12-064626v1 110/3/986    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 Ciurea, S. O. Articles by Hoffman, R. Search for Related Content PubMed PubMed Citation Articles by Ciurea, S. O. Articles by Hoffman, R. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis Stefan O. Ciurea1, Delwin Merchant1, Nadim Mahmud1, Takefumi Ishii1, Yan Zhao1, Wenyang Hu1, Edward Bruno1, Giovanni Barosi2,3, Mingjiang Xu1,3, and Ronald Hoffman1,3 1 University of Illinois College of Medicine at Chicago, Hematology/Oncology Section, Department of Medicine, Chicago; 2 Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; 3 Myeloproliferative Diseases Research Consortium, New York, NY In order to investigate the biologic processes underlying and resulting from the megakaryocytic hyperplasia that characterizes idiopathic myelofibrosis (IMF), peripheral blood CD34+ cells isolated from patients with IMF, polycythemia vera (PV), and G-CSF–mobilized healthy volunteers were cultured in the presence of stem cell factor and thrombopoietin. IMF CD34+ cells generated 24-fold greater numbers of megakaryocytes (MKs) than normal CD34+ cells. IMF MKs were also shown to have a delayed pattern of apoptosis and to overexpress the antiapoptotic protein bcl-xL. MK hyperplasia in IMF is, therefore, likely a consequence of both the increased ability of IMF progenitor cells to generate MKs and a decreased rate of MK apoptosis. Media conditioned (CM) by CD61+ cells generated in vitro from CD34+ cells were then assayed for the levels of growth factors and proteases. Higher levels of transforming growth factor-ß (TGF-ß) and active matrix metalloproteinase-9 (MMP9) were observed in media conditioned with IMF CD61+ cells than normal or PV CD61+ cells. Both normal and IMF CD61+ cells produced similar levels of VEGF. MK-derived TGF-B and MMP-9, therefore, likely contribute to the development of many pathological epiphenomena associated with IMF. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Chronic megakaryocytic leukemia, misnamed chronic idiopathic myelofibrosis, has neoplastic not hyperplastic megakaryocytopoiesis Marshall A. Lichtman Blood 2007 110: 3085-3086. [Full Text] [PDF] This article has been cited by other articles: X. Wang, W. Zhang, T. Ishii, S. Sozer, J. Wang, M. Xu, and R. Hoffman Correction of the Abnormal Trafficking of Primary Myelofibrosis CD34+ Cells by Treatment with Chromatin-Modifying Agents Cancer Res., October 1, 2009; 69(19): 7612 - 7618. [Abstract] [Full Text] [PDF] J. M. Gozgit, G. Bebernitz, P. Patil, M. Ye, J. Parmentier, J. Wu, N. Su, T. Wang, S. Ioannidis, A. Davies, et al. Effects of the JAK2 Inhibitor, AZ960, on Pim/BAD/BCL-xL Survival Signaling in the Human JAK2 V617F Cell Line SET-2 J. Biol. Chem., November 21, 2008; 283(47): 32334 - 32343. [Abstract] [Full Text] [PDF] L. Zhou, A. N. Nguyen, D. Sohal, J. Ying Ma, P. Pahanish, K. Gundabolu, J. Hayman, A. Chubak, Y. Mo, T. D. Bhagat, et al. 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