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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4508-4515. Prepublished online as a Blood First Edition Paper on February 10, 2005; DOI 10.1182/blood-2004-08-3238. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3238v1 105/11/4508    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 Xu, M. Articles by Hoffman, R. Search for Related Content PubMed PubMed Citation Articles by Xu, M. Articles by Hoffman, R. Related Collections Hematopoiesis and Stem Cells Neoplasia Cell Adhesion and Motility Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases Mingjiang Xu, Edward Bruno, Joseph Chao, Stephen Huang, Guido Finazzi, Steven M. Fruchtman, Uday Popat, Josef T. Prchal, Giovanni Barosi, Ronald Hoffman, for the MPD Research Consortium From the Section of Hematology/Oncology, University of Illinois at Chicago Cancer Center, University of Illinois College of Medicine, Chicago, IL; the Department of Hematology, Ospedali Riuniti, Bergamo, Italy; the Mount Sinai School of Medicine, New York, NY; the Baylor College of Medicine, Houston, TX; The Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, Italy. Idiopathic myelofibrosis (IM) is characterized by increased numbers of CD34+ cells in the peripheral blood (PB). We explored the possible mechanisms underlying this abnormal trafficking of CD34+ cells. Plasma levels of neutrophil elastase (NE), total and active matrix metalloproteinase 9 (MMP-9), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were dramatically increased in IM. The absolute number of CD34+ cells in the PB was correlated with the levels of sVCAM-1. Marked elevations of the levels of NE but not total and active MMP-9 as well as MMP-2 were detected in media conditioned by IM mononuclear cells (MNCs) as compared with that of healthy volunteers. IM MNC-conditioned media, however, was shown by zymographic analysis to contain increased gelatinolytic activity corresponding to the molecular weight of MMP-9. IM MNC-conditioned media also exhibited a greater ability to cleave VCAM-1 and c-kit in vitro, consistent with the biologic actions of NE. In addition, the increased ability of IM PB CD34+ cells to migrate through a reconstituted basement membrane was diminished by several inhibitors of MMP-9 activity, indicating that these cells express increased levels of this MMP. These data indicate that a proteolytic environment exists in IM which might result in the sustained mobilization of CD34+ cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Y. Cho, J. Roboz, M. Xu, and R. Hoffman Primary Myelofibrosis Is Associated with Truncation of the Plasma Chemokine SDF-1 Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 3731 - 3731. [Abstract] 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] J. Shi, Y. Zhao, T. Ishii, W. Hu, S. Sozer, W. Zhang, E. Bruno, V. Lindgren, M. Xu, and R. Hoffman Effects of Chromatin-Modifying Agents on CD34+ Cells from Patients with Idiopathic Myelofibrosis Cancer Res., July 1, 2007; 67(13): 6417 - 6424. [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] P. Guglielmelli, R. Zini, C. Bogani, S. Salati, A. Pancrazzi, E. Bianchi, F. Mannelli, S. Ferrari, M.-C. Le Bousse-Kerdiles, A. Bosi, et al. Molecular Profiling of CD34+ Cells in Idiopathic Myelofibrosis Identifies a Set of Disease-Associated Genes and Reveals the Clinical Significance of Wilms' Tumor Gene 1 (WT1) Stem Cells, January 1, 2007; 25(1): 165 - 173. [Abstract] [Full Text] [PDF] O. Bock, J. Neuse, K. Hussein, K. Brakensiek, G. Buesche, T. Buhr, B. Wiese, and H. Kreipe Aberrant Collagenase Expression in Chronic Idiopathic Myelofibrosis Is Related to the Stage of Disease but Not to the JAK2 Mutation Status Am. J. Pathol., August 1, 2006; 169(2): 471 - 481. [Abstract] [Full Text] [PDF] R. Hoffman and M. Xu Is bone marrow fibrosis the real problem? Blood, May 1, 2006; 107(9): 3421 - 3422. [Full Text] [PDF] F. Passamonti, E. Rumi, D. Pietra, M. G. D. Porta, E. Boveri, C. Pascutto, L. Vanelli, L. Arcaini, S. Burcheri, L. Malcovati, et al. Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders Blood, May 1, 2006; 107(9): 3676 - 3682. [Abstract] [Full Text] [PDF] U. Popat, A. Frost, E. Liu, Y. Guan, A. Durette, V. Reddy, and J. T. Prchal High levels of circulating CD34 cells, dacrocytes, clonal hematopoiesis, and JAK2 mutation differentiate myelofibrosis with myeloid metaplasia from secondary myelofibrosis associated with pulmonary hypertension Blood, May 1, 2006; 107(9): 3486 - 3488. [Abstract] [Full Text] [PDF] R. L. Levine and G. Wernig Role of JAK-STAT Signaling in the Pathogenesis of Myeloproliferative Disorders Hematology, January 1, 2006; 2006(1): 233 - 239. [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] M. Xu, E. Bruno, H. Ni, V. Rosti, M. Massa, G. Barosi, and R. Hoffman SDF-1/CXCR4 Interactions in Idiopathic Myelofibrosis. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 3504 - 3504. [Abstract] 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]

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