Studies on megakaryopoiesis in patients with myelodysplasia and idiopathic thrombocytopenic purpura Houwerzijl, Ewout Johan

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1 University of Groningen Studies on megakaryopoiesis in patients with myelodysplasia and idiopathic thrombocytopenic purpura Houwerzijl, Ewout Johan IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2008 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Houwerzijl, E. J. (2008). Studies on megakaryopoiesis in patients with myelodysplasia and idiopathic thrombocytopenic purpura s.n. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 Studies on megakaryopoiesis in patients with myelodysplasia and idiopathic thrombocytopenic purpura Ewout Houwerzijl

3 CIP-GEGEVENS KONINKLIJKE BIBLIOTHEEK, DEN HAAG Houwerzijl, E.J. Studies on megakaryopoiesis in patients with myelodysplasia and idiopathic thrombocytopenic purpura. Proefschrift Groningen. Met lit.opg. Met samenvatting in het Nederlands. ISBN Copyright 2008 E.J. Houwerzijl All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanically, by photocopying, recording or otherwise, without the written permission from the author. Cover: Dr. Paul Gottlieb Werlhof ( ), German physician, poet and composer. In 1735 he described a patient with morbus maculosus haemorrhagicus, a disorder nowadays known as idiopathic thrombocytopenic purpura or Werlhof s disease. Portrait courtesy of the DGHO Deutsche Gesellschaft für Hämatologie und Onkologie ( Printed by: Gildeprint Drukkerijen BV, Enschede, the Netherlands Financial support for the publication of this thesis was kindly provided by Amgen BV, Breda; MSD; Pfizer BV; Schering-Plough BV; Servier Nederland Farma BV; Zambon Nederland BV en de Stichting ter Bevordering van de Haematologie Groningen

4 RIJKSUNIVERSITEIT GRONINGEN Studies on megakaryopoiesis in patients with myelodysplasia and idiopathic thrombocytopenic purpura Proefschrift ter verkrijging van het doctoraat in de Medische Wetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op woensdag 6 februari 2008 om uur door Ewout Johan Houwerzijl geboren op 14 februari 1970 te Groningen

5 Promotor: Prof.dr. E. Vellenga Copromotores: Dr. J.J.L. van der Want Dr. J.Th.M. de Wolf Beoordelingscommissie: Prof.dr. J. van der Meer Prof.dr. G.E.G. Verhoef Prof.dr.Th.J.M. de Witte

6 Paranimfen: Gert-Jan Braunstahl Erwin Nijsse

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8 CONTENTS Chapter I Introduction 9 Chapter II Chapter III Chapter IV Chapter V Chapter VI Chapter VII Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death Leukemia. 2006;20: Increased peripheral platelet destruction and caspase-3-independent programmed cell death of bone marrow megakaryocytes in myelodysplastic patients Blood. 2005;105: Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy Submitted for publication Increased glycocalicin-index and normal thrombopoietin levels in patients with idiopathic thrombocytopenic purpura with a decreased rate of platelet production Haematologica. 2005;90: Ultrastructural study shows morphological features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura Blood. 2004;103: Platelet production rate predicts the response to prednisone in patients with idiopathic thrombocytopenic purpura Submitted for publication Chapter VIII Summary, conclusions and future perspectives 137 Chapter IX Nederlandse samenvatting 149 List of abbreviations 157 Dankwoord 161

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