Normal and malignant B-cells in acute lymphoblastic leukemia

218 Pages·2016·23.92 MB·English

Normal and malignant
B-cells in acute
lymphoblastic leukemia
Insight into clonal distrubution,
minimal residual disease
and normal B-cell recovery
Prisca M.J. Theunissen
The research for this thesis was performed within the framework of the
Erasmus Postgraduate School Molecular Medicine.
The studies described in the thesis were performed at the Department of
Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam,
The Netherlands and collaborating institutions.
The studies were financially supported by ERA-NET PrioMedChild, project
40-41800-98-027.
The printing of this thesis was supported by Erasmus MC.
ISBN: 978-94-91811-15-9
Illustrations: Prisca Theunissen
Cover: Prisca Theunissen
Lay-out: Daniëlle Korpershoek, Erna Moerland and
Bibi van Bodegom
Printing: Haveka B.V., Alblasserdam, the Netherlands
Copyright © 2016 by Prisca Theunissen. All rights reserved.
No part of this book may be reproduced, stored in a retrieval system or
transmitted in any form or by any means, without prior permission of the
author.
Normal and malignant B-cells
in acute lymphoblastic leukemia
Insight into clonal distribution, minimal residual
disease and normal B-cell recovery
Normale en maligne B-cellen in acute lymfoblastische leukemie
Inzicht in klonale distributie, minimale restziekte en herstel van normale B-cellen
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 21 december 2016 om 13.30 uur
door
Prisca Maria Josephina Theunissen
geboren te Bilzen, België
ProMoTIe coMMIssIe
Promotoren
Prof.dr. J.J.M. van Dongen
overige leden
Dr. M. van der Burg
Prof.dr. T. Szczepański
Prof.dr. C.M. Zwaan
copromotor
Dr. V.H.J. van der Velden

coNTeNTs
chaPTer 1 9
General introduction
chaPTer 2 31
Antigen receptor sequencing of paired bone marrow samples shows
homogeneous distribution of acute lymphoblastic leukemia subclones
Submitted
chaPTer 3 63
Understanding the reconstitution of the B-cell compartment in
bone marrow and blood after treatment for B-cell precursor
acute lymphoblastic leukemia
Submitted to Br J Haematol (minor revisions)
chaPTer 4 89
Detailed immunophenotypic analysis of B-cell precursors in
regenerating bone marrow of children treated for acute lympho-
blastic leukemia reveals new subsets: implications for minimal
residual disease detection
Submitted
chaPTer 5 113
Pattern of expression of CD73, CD86 and CD304 in normal vs.
leukemic B-cell precursors: utility as stable minimal residual disease
markers for treatment monitoring in childhood B-cell precursor acute
lymphoblastic leukemia
Submitted
chaPTer 6 143
Standardized flow cytometry for highly sensitive MRD measurements
in B-cell acute lymphoblastic leukemia
Accepted for publication in Blood
chaPTer 7 181
General discussion
addeNduM 199
Abbreviations 201
Summary 203
Samenvatting 207
Dankwoord 211
Curriculum Vitae 213
PhD Portfolio 215
Publications 217

chapter 1
General Introduction