University of Groningen Dysregulation of transcription and cytokine networks in Hodgkin lymphomas with a focus on nodular lymphocyte predominance type of Hodgkin lymphoma Atayar, Cigdem 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: 2006 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Atayar, C. (2006). Dysregulation of transcription and cytokine networks in Hodgkin lymphomas with a focus on nodular lymphocyte predominance type of Hodgkin lymphoma [S.l.]: [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): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 20-01-2019
Dysregulation of transcription and cytokine networks in Hodgkin lymphomas with a focus on nodular lymphocyte predominance type of Hodgkin lymphoma Çiğdem Atayar
ISBN 90-367-2653-0 Copyright by Çiğdem Atayar, 2006 All rights reserved. No part of this publication may be reproduced, or transmitted in any form or by any means, without permission of the author. Cover Impression Hodgkin lymphoma, Hazal Rona Azizoğlu (10), daughter of Çiğdem Atayar Printed by PrintPartners Ipskamp B.V., Enschede, The Netherlands 2
RIJKSUNIVERSITEIT GRONINGEN DYSREGULATION OF TRANSCRIPTION AND CYTOKINE NETWORKS IN HODGKIN LYMPHOMAS with a focus on nodular lymphocyte predominance type of Hodgkin lymphoma 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 5 juli 2006 om 13.15 uur door Çiğdem Atayar geboren op 13 december 1969 te Diyarbakır, Turkije 3
Promotor: Prof. Dr. S. Poppema Copromotores: Dr. J.H.M. van den Berg Dr. L. Visser Beoordelingscommissie: Prof. Dr. P. M. Kluin Prof. Dr. R. Jarret Prof. Dr. R. Küppers 4
Paranimfen: J. Kluiver T. Blokzijl The work described in this study was carried out mainly at the Department of Pathology and Laboratory Medicine, University Medical Centre Groningen, University of Groningen, The Netherlands. The studies described in this thesis were financially supported by Groningen University Institute for Drug Exploration (Grant 944507) and Jan Kornelius de Cock Foundation. The printing of this thesis is financially supported by Groningen University Institute for Drug Exploration; Faculty of Medical Sciences, University of Groningen; Department of Pathology and Laboratory Medicine, University Medical Centre Groningen. 5
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To my parents Anneme ve babama 7
Abbreviations ABR acgh APC APES BAC CGH chl CSR CT D-LPHL DAB DRC EDTA ETFL FICTION FISH FL GC HL HRP HRS L&H LBCL LRcHL LD Mb MBR MC NLPHL NS PAC PTGC qpcr SHM TF T H alternative breakpoint region array-based comparative genomic hybridization antigen presenting cell aminopropyltriethoxysilane bacterial artificial chromosome comparative genomic hybridization classical Hodgkin lymphoma class switch recombination threshold cycle diffuse lymphocyte predominance type of Hodgkin lymphoma 3,3'- diaminobenzidine dendritic reticulum cell ethylenediaminetetraacetic acid European Task Force on Lymphoma fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms fluorescence in situ hybridization follicular lymphoma germinal centre Hodgkin lymphoma horseradish peroxidase Hodgkin and Reed-Sternberg lymphocytic and histiocytic large B-cell lymphoma lymphocyte rich classical Hodgkin lymphoma lymphocyte depleted megabase major breakpoint region mixed cellularity nodular lymphocyte predominance type of Hodgkin lymphoma nodular sclerosis P1-based artificial chromosome progressively transformed germinal centres quantitative PCR somatic hypermutation transcription factor T-helper T/HRBCL T-cell/histiocyte rich B-cell lymphoma T R T regulatory 8
Contents Abbreviations 8 The scope of this thesis 11 Chapter 1 Nodular lymphocyte predominance type of Hodgkin lymphoma In Diagnostic Hematopathology. Edited by Jaffe ES, Harris NL, Vardiman J. Harcourt Health Sciences, Oxford 2006 in press 13 Chapter 2 BCL6 ABR break and homozygous deletion of 17q24 in the nodular lymphocyte predominance type Hodgkin lymphoma derived cell line DEV Hum Path 2006, In Press 73 Chapter 3 Hodgkin lymphoma associated T-cells exhibit a transcription factor profile consistent with distinct lymphoid compartments Submitted 93 Chapter 4 Expression of the T-cell transcription factors, GATA3 and T-bet, in the neoplastic cells of Hodgkin lymphomas Am J Pathol. 2005 Jan;166(1):127-34 111 Chapter 5 Cytokine gene expression profile distinguishes CD4 + /CD57 + T-cells of nodular lymphocyte predominance type of Hodgkin lymphoma from their tonsillar counterparts J Pathol. 2006 Feb;208(3):423-30 133 Summary and concluding remarks 151 Nederlandse samenvatting 159 Curriculum vitae 165 Publications 167 Dankwoord 169 Colour figures 175 9
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