SEARCH:   Advanced

Blood, 12 February 2009, Vol. 113, No. 7, pp. 1535-1542. Prepublished online as a Blood First Edition Paper on November 24, 2008; DOI 10.1182/blood-2008-08-172338. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-08-172338v1 113/7/1535    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 Veljkovic, D. K. Articles by Hayward, C. P. M. Search for Related Content PubMed PubMed Citation Articles by Veljkovic, D. K. Articles by Hayward, C. P. M. Related Collections Platelets and Thrombopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation D. Kika Veljkovic1, Georges E. Rivard2, Maria Diamandis1, Jessica Blavignac1, Elisabeth M. Cramer-Bordé3, and Catherine P. M. Hayward1,4 1 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON; 2 Division of Hematology/Oncology, Centre Hôspitalier Universitaire Sainte Justine, Montreal, QC; 3 Faculté de Médecine Paris-Ile de France-Ouest, Université de Versailles-St Quentin and Département d'Hématologie, Institut Cochin, Paris, France; and 4 Department of Medicine, McMaster University, Hamilton, ON Quebec platelet disorder (QPD) is an inherited bleeding disorder associated with increased urokinase plasminogen activator (uPA) in platelets but not in plasma, intraplatelet plasmin generation, and -granule protein degradation. These abnormalities led us to investigate uPA expression by QPD CD34+ progenitors, cultured megakaryocytes, and platelets, and whether uPA was stored in QPD -granules. Although QPD CD34+ progenitors expressed normal amounts of uPA, their differentiation into megakaryocytes abnormally increased expression of the uPA gene but not the flanking genes for vinculin or calcium/calmodulin-dependent protein kinase II on chromosome 10. The increased uPA production by cultured QPD megakaryocytes mirrored their production of -granule proteins, which was normal. uPA was localized to QPD -granules and it showed extensive colocalization with -granule proteins in both cultured QPD megakaryocytes and platelets, and with plasminogen in QPD platelets. In QPD megakaryocytes, cultured without or with plasma as a source of plasminogen, -granule proteins were stored undegraded and this was associated with much less uPA-plasminogen colocalization than in QPD platelets. Our studies indicate that the overexpression of uPA in QPD emerges with megakaryocyte differentiation, without altering the expression of flanking genes, and that uPA is costored with -granule proteins prior to their proteolysis in QPD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Diamandis, A. D. Paterson, J. M. Rommens, D. K. Veljkovic, J. Blavignac, D. E. Bulman, J. S. Waye, F. Derome, G. E. Rivard, and C. P. M. Hayward Quebec platelet disorder is linked to the urokinase plasminogen activator gene (PLAU) and increases expression of the linked allele in megakaryocytes Blood, February 12, 2009; 113(7): 1543 - 1546. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020