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

183 Pages·2013·12.52 MB·English

by  Marjolein Blink

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Marjolein Blink

CliniCal RelevanCe of GenetiC alteRations
in aCute Myeloid leukeMia in
ChildRen with down syndRoMe
Marjolein Blink
Clinical Relevance of Genetic alterations in acute Myeloid leukemia in Children with
down syndrome
Copyright © 2013 Marjolein Blink, amsterdam, the netherlands
isBn: 978-94-6169-443-0
Photo cover: wouter knaack
Printing: optima Grafische Communicatie, Rotterdam
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 publications.
the work described in this thesis was performed at the department of Pediatric oncol-
ogy/ hematology of the erasmus MC- sophia Children’s hospital, Rotterdam, the neth-
erlands. this work was funded by the sophia foundation and kika (stichting kinderen
kankervrij).
Printing of this thesis was financially supported by the Pediatric oncology foundation
Rotterdam (koCR), the erasmus university Rotterdam and Boehringer ingelheim bv.
CliniCal RelevanCe of GenetiC
alteRations in aCute Myeloid leukeMia
in ChildRen with down syndRoMe
klinisChe Relevantie van GenetisChe
afwijkinGen Bij aCute Myeloïde leukeMie
Bij kindeRen Met down syndRooM
PRoefsChRift
ter verkrijging van de graad van doctor aan de
erasmus universiteit Rotterdam
op gezag van de rector magnificus
Prof. dr. h.G. schmidt
en volgens het besluit van het College voor Promoties.
de openbare verdediging zal plaatsvinden op
woensdag 6 november 2013 om 13.30 uur door
Marjolein Blink
geboren te Groningen
PRoMotieCoMMissie:
Promotor: Prof. dr. R. Pieters
overige leden: Prof. dr. j.j.M. van dongen
Prof. dr. P. sonneveld
Prof. dr. G.j.l. kaspers
Copromotoren: dr. C.M. Zwaan
dr. M.M. van den heuvel- eibrink
Contents

ChaPteR 1 General introduction 7
ChaPteR 2 high frequency of copy number alterations in 27
myeloid leukaemia of down syndrome
ChaPteR 3 frequency and prognostic implications of JAK 1-3 43
aberrations in down syndrome acute lymphoblastic
and myeloid leukemia
ChaPteR 4 low frequency of type-i and type-ii aberrations in 55
myeloid leukemia of down syndrome: underscoring
the unique entity of this disease
ChaPteR 5 normal karyotype is a poor prognostic factor in 65
myeloid leukemia of down syndrome: a retrospective
international study
ChaPteR 6 Gene expression profiling in transient 85
myeloproliferative disorder and myeloid leukemia of
down syndrome
ChaPteR 7 summary, general discussion and future perspectives 105
ChaPteR 8 nederlandse samenvatting 127
aBout the authoR Curriculum vitae 135
list of Publications 137
Phd Portfolio 139
dankwoord/ acknowledgements 141
aPPendiCes supplementary data 146
Color figures 155
abbreviations 177
affiliations co-authors 179

ChaPteR 1
GeneRal intRoduCtion