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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3472-3479. Prepublished online as a Blood First Edition Paper on November 12, 2004; DOI 10.1182/blood-2004-06-2108. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2108v1 105/9/3472    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 Houwerzijl, E. J. Articles by de Wolf, J. Th. M. Search for Related Content PubMed PubMed Citation Articles by Houwerzijl, E. J. Articles by de Wolf, J. Th. M. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Neoplasia Apoptosis Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Increased peripheral platelet destruction and caspase-3–independent programmed cell death of bone marrow megakaryocytes in myelodysplastic patients Ewout J. Houwerzijl, Nel R. Blom, Johannes J. L. van der Want, Henk Louwes, Mariet T. Esselink, Jan W. Smit, Edo Vellenga, and Joost Th. M. de Wolf From the Department of Hematology, University Hospital Groningen, Groningen, the Netherlands; the Department of Cell Biology, Section for Electron Microscopy, University of Groningen, Groningen, the Netherlands; and Nuclear Medicine, Martini Hospital, Groningen, the Netherlands. To investigate underlying mechanisms of thrombocytopenia in myelodysplastic syndrome (MDS), radiolabeled platelet studies were performed in 30 MDS patients with platelet counts less than 100 x 109/L. Furthermore, plasma thrombopoietin and glycocalicin index (a parameter of platelet or megakaryocyte destruction) were determined. Mean platelet life (MPL), corrected for the degree of thrombocytopenia, was reduced in 15 of 30 patients (4.3 ± 0.9 days [mean ± SD] vs 6.0 ± 1.3, P = .0003). Platelet production rate (PPR) was reduced in 25 of 30 patients (68 ± 34 x 109/d vs 220 ± 65, P < .0001). Thrombopoietin levels were not significantly correlated with the PPR. However, the glycocalicin index was significantly higher compared with controls (15 ± 16 vs 0.7 ± 0.2, P = .001) and significantly correlated with the PPR (P = .02, r = -0.5), but not with the MPL (P = 1.8). Ultrastructural studies demonstrated necrosis-like programmed cell death (PCD) in mature and immature megakaryocytes (n = 9). Immunohistochemistry of the bone marrow biopsies demonstrated no positive staining of MDS megakaryocytes for activated caspase-3 (n = 24) or cathepsin D (n = 21), while activated caspase-8 was demonstrated in a subgroup of patients (5/21) in less than 10% of megakaryocytes. These results indicate that the main cause of thrombocytopenia in MDS is caspase-3–independent necrosis-like PCD resulting in a decreased PPR in conjunction with an increased glycocalicin index. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Catastrophic for contaminated chickens, murder on mutant mice: harmful to human hematopoiesis? David P. Steensma Blood 2005 105: 3389-3390. [Full Text] [PDF] This article has been cited by other articles: I. Penna, H. Du, R. Ferriani, and H. S. Taylor Calpain5 expression is decreased in endometriosis and regulated by HOXA10 in human endometrial cells Mol. Hum. Reprod., October 1, 2008; 14(10): 613 - 618. [Abstract] [Full Text] [PDF] G. M. Fuhler, N. R. Blom, P. J. Coffer, A. L. Drayer, and E. Vellenga The reduced GM-CSF priming of ROS production in granulocytes from patients with myelodysplasia is associated with an impaired lipid raft formation J. Leukoc. Biol., February 1, 2007; 81(2): 449 - 457. [Abstract] [Full Text] [PDF] A. Agool, B. W. Schot, P. L. Jager, and E. Vellenga 18F-FLT PET in Hematologic Disorders: A Novel Technique to Analyze the Bone Marrow Compartment J. Nucl. Med., October 1, 2006; 47(10): 1592 - 1598. [Abstract] [Full Text] [PDF]

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