Clinical Relevance of Genetic Alterations in Acute Lymphoblastic Leukemia in Children with Down ...

204 Pages·2014·3.74 MB·English

by  Trudy Buitenkamp

Clinical Relevance of Genetic Alterations
in Acute Lymphoblastic Leukemia in
Children with Down syndrome
Trudy BuiTenkamp
Clinical relevance of Genetic alterations in acute Lymphoblastic Leukemia in Children
with down syndrome
Copyright © T.D. Buitenkamp, the Netherlands 2014
Cover: Trudy Buitenkamp, Mieke Fraussen
Printed by: Optima Grafische Communicatie Rotterdam
ISBN/EAN: 978-94-6169-522-2
No part of this thesis may be reproduced, stored in a retrieval system or transmitted in any
form or by any means, without written permission of the author or, when appropriate, of the
publishers of t he publications.
The work described in this thesis was performed at the Department of Paediatric Oncology/
Haematology of the Erasmus Medical Centrum, Sophia Children’s Hospital, Rotterdam, the
Netherlands. This work was funded by KinderenKankervrij (KIKA) and the Paediatric Oncol-
ogy Foundation Rotterdam (KOCR)
Publication of this thesis was financially supported by:
Erasmus Universtity Rotterdam, Stichting Kinderoncologisch Centrum Rotterdam, MRC Hol-
land and AMGEN BV.
MRC-Holland
MLPA®
Clinical Relevance of Genetic Alterations in
Acute Lymphoblastic Leukemia in Children
with Down syndrome
Klinische relevantie van genetische afwijkingen in Acute
Lymfatische Leukemie bij kinderen met het syndroom
van Down.
Proefschrift
Ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de rector magnificus
Prof.dr. H.A.P. Pols
en volgens besluit van het college voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 2 juli 2014 om 15: 30 uur
Door
Trudy Dina Buitenkamp
geboren te Ten Post
prOmOTieCOmmiSSie:
Promotor: Prof.dr. R. Pieters
Overige leden: Prof.dr. M.L den Boer
Prof.dr. P.C. Huijgens
Dr. M.W.J. Fornerod
Copromotoren: Dr. C.M. Zwaan
Dr. M.M. van de Heuvel-Eibrink
“Life isn’t about waiting for the storm to pass,
it’s learning to dance in the rain.”
Voor Martijn & Sterre

COnTenTS
Chapter 1. General Introduction 9
Chapter 2. Acute Lymphoblastic Leukemia in children with Down syndrome: a retrospective 23
analysis from the Ponte di Legno study group
Blood. 2014 Jan 2; 123(1): 70-7
Chapter 3. Methotrexate-induced side effects are not due to differences in pharmacokinetics In 49
children with Down syndrome and Acute Lymphoblastic Leukemia
Haematologica. 2010 Jul; 95(7):1 106-13
Chapter 4. Frequency and prognostic implications of JAK 1-3 aberrations in Down syndrome acute 69
lymphoblastic and myeloid leukemias
Leukemia. 2011 Aug; 25(8):1 365-8
Chapter 5. Outcome in children with Down syndrome and Acute Lymphoblastic Leukemia and 85
IKZF1 deletions and CRLF2 aberrations
Leukemia. 2012 Oct; 26(10):2 204-11
Chapter 6. BTG1 deletions do not predict outcome in Down syndrome Acute Lymphoblastic 119
leukemia
Leukemia. 2013 Jan; 27(1):2 51-2
Chapter 7. Down syndrome acute lymphoblastic leukemia is characterized by loss of ETS-related 127
gene (ERG) repression
Manuscript in preparation
Chapter 8. General Discussion and Future Perspectives 151
Chapter 9. Summary Samenvatting 173
Chapter 10. About the author 185
Curriculum Vitae 187
List of publications 189
PhD Portfolio 191
Dankwoord 193
Affiliations co-authors 201
List of abbreviations 197

1
General Introduction