Citation for published version (APA): Cate, B. T. (2010). Targeted apoptosis induction in hemato-oncology Groningen: s.n.

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1 University of Groningen Targeted apoptosis induction in hemato-oncology Cate, Bram ten 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: 2010 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Cate, B. T. (2010). Targeted apoptosis induction in hemato-oncology Groningen: 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 The research described in this thesis was financially supported by grants from the Dutch Cancer Society (RUG ) and the Jan Kornelis de Cock Foundation. The author gratefully acknowledges the financial support for printing of this thesis by: MosaMedix Health Care BD Biosciences BV Nederland J.E. Jurriaanse Stichting University of Groningen Stichting Contactgroep Leukemie University Medical Center Groningen Graduate School for Drug Exploration Cover design: Layout design: Printed by: Marc Daalmans & Bram ten Cate Guido Krenning & Bram ten Cate Ipskamp drukkers B.V. ISBN: (printed version) ISBN: (digital version) 2010 by Bram ten Cate All right reserved. No part of this publication may be reproduced, or transmitted in any form or by any means without premission of the author and the publisher holding the copyrights of the articles

3 Targeted Apoptosis Induction in Hemato-Oncology 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 17 maart 2010 om 16:15 uur door Bram ten Cate geboren op 28 augustus 1981 te Hattem

4 Promotor: Prof. dr. L.F.M.H. de Leij Copromotor: Dr. W. Helfrich Beoordelingscommissie: Prof. dr. E. Vellenga Prof. dr. G.J. Ossenkoppele Prof. dr. W.J. Quax

5 Education is what remains after one has forgotten what one has learned in school. Albert Einstein voor Pap & Mam

6 Paranimfen: Theo Bijma Wing Ho Chung

7 Contents Chapter 1: introduction to the thesis CHAPTER 2: CD7-restricted activation of FAS-mediated apoptosis: A novel therapeutic approach for acute t-cell leukemia chapter 3: Fas Receptor Clustering and Involvement of the Death Receptor Pathway in Rituximab-Mediated Apoptosis with Concomitant Sensitization of Lymphoma B Cells to Fas-Induced Apoptosis CHapter 4: Superior activity of fusion protein scfvrit:sfasl over COTREATMENT with rituximab and Fas agonists 59 chapter 5: The histone deacetylase inhibitor valproic acid potently AUGMENTS gemtuzumab ozogamicin-induced apoptosis in Acute Myeloid Leukemic cells 75 chapter 6: A novel AML-selective TRAIL fusion protein that is SUPERIOR to Gemtuzumab Ozogamicin in terms of in vitro SELECTIVITy, activity, and stability 85 chapter 7: Targeted elimination of leukemia stem cells; A new therapeutic approach in hemato-oncology chapter 8: Targeting of Acute Myeloid Leukemia (AML) Stem Cells by SCFv:Death Ligand fusion proteins with designed specificity for C-type Lectin-LIKE Molecule-1 (CLL-1) chapter 9: Summary and PerSpectives 145 chapter 10: Nederlandse Samenvatting BIOGRAPHY AND list of Publications Dankwoord

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