molecular genetic aberrations and their prognostic relevance in pediatric acute myeloid leukemia

230 Pages·2016·27.49 MB·English

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Juliana van Stolberglaan 5R
2595CA ‘s Gravenhage
[email protected]

Paranimfen
Rozemarijn de Rooij
Floor Verhagen
[email protected]
2016
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Molecular genetic aberrations and their prognostic relevance
in pediatric acute myeloid leukemia
Moleculaire genetische afwijkingen en hun prognostische relevantie
in acute myeloïde leukemie bij kinderen
Jasmijn D.E. de Rooij
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Molecular aberrations and their prognostic relevance in pediatric acute myeloid
leukemia.
Copyright © 2016 Jasmijn de Rooij, ‘s Gravenhage, The Netherlands
ISBN: 978-94-6299-334-1
Cover design and illustrations: Lisette Grove
Lay-out: Jasmijn de Rooij
Printing: Ridderprint BV
Photography: Dagmara Domenicus www.foto-dag.nl
A very special thank you to Diane en Jan Peter Veeneman.
No part of this thesis may be reproduced, stored in a retrieval system or transmitted in
any form or by any means without permission from the author or, when appropriate,
from the publishers of the publication.
The work described in this thesis was performed at the Department of Pediatric
Oncology/Hematology of the Erasmus MC-Sophia Children’s Hospital, Rotterdam,
the Netherlands. This work was funded by stichting Kinderoncologisch Centrum
Rotterdam (KOCR).
Electronic version
available via QR-code
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Molecular genetic aberrations and their prognostic relevance
in pediatric acute myeloid leukemia
Moleculaire genetische afwijkingen en hun prognostische relevantie
in acute myeloïde leukemie bij kinderen
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
dinsdag 14 juni 2016 om 13:30 uur
door Jasmijn Diantha Eliane de Rooij
geboren te Leiden

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Promotiecommissie
Promotoren: Prof.dr. C.M. Zwaan
Prof.dr. R. Pieters
Copromotor: Dr. M.M. van den Heuvel-Eibrink
Overige leden: Prof.dr. I.P. Touw
Prof.dr. D. Reinhardt
Prof.dr. R.M.W. Hofstra 
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Contents
Chapter 1 General introduction 7

Part one Molecular insights in pediatric acute megakaryoblastic leukemia 25
Chapter 2 NUP98/JARID1A is a novel recurrent abnormality in pediatric acute 27
megakaryoblastic leukemia with a distinct HOX-gene expression pattern
Chapter 3 RB1 loss as a unique and universally required additional hit in 51
NUP98/KDM5A rearranged acute megakaryoblastic leukemia
Chapter 4 Pediatric non-Down syndrome acute megakaryoblastic leukemia is 73
characterized by distinct genomic subsets with varying outcomes
Chapter 5 Recurrent genetic abnormalities can be used for risk-group 91
stratification in pediatric AMKL: results of a retrospective intergroup
study
Part two Aberrations and translocations in pediatric acute myeloid leukemia 111
Chapter 6 ETV6 aberrations are recurrent in pediatric acute myeloid leukemia 113
Chapter 7 Recurrent deletions of IKZF1 in pediatric acute myeloid leukemia 133
Chapter 8 BCOR and BCORL1 mutations in pediatric acute myeloid leukemia 155
Chapter 9 PHF6 mutations in pediatric acute myeloid leukemia 167
Chapter 10 Recurrent translocation t(10;17)(p15;q21) in minimally differentiated 179
acute myeloid leukemia results in ZMYND11/MBTD1 fusion
Chapter 11 Summary 191
Samenvatting 197

Chapter 12 Discussion 207
Chapter 13 About the author 217
Curriculum vitae
List of publications
PhD portfolio
Dankwoord
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Chapter 1: General introduction
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Chapter 1
General introduction
Adapted from:
Pediatric AML: From Biology to Clinical Management
Jasmijn D. E. de Rooij, C. Michel Zwaan and Marry van den Heuvel-Eibrink
Journal of Clinical Medicine 2015 Jan 9;4(1):127-149.
7
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Chapter 1: General introduction
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