Extrinsic and intrinsic cues involved in BCR-ABL induced leukemogenesis Sontakke, Pallavi

149 Pages·2016·14.61 MB·English

University of Groningen

Extrinsic and intrinsic cues involved in BCR-ABL induced leukemogenesis
Sontakke, Pallavi
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Sontakke, P. (2016). Extrinsic and intrinsic cues involved in BCR-ABL induced leukemogenesis:
Establishing an ectopic humanized niche xenograft model and the study of metabolic alterations in chronic
myeloid leukemia. [Thesis fully internal (DIV), University of Groningen]. University of Groningen.
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Download date: 20-01-2023
Extrinsic and intrinsic cues involved in
BCR-ABL induced leukemogenesis

Pallavi Sontakke

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Research presented in this thesis was financially supported by:
Dutch Cancer Society

Printing of this thesis was financially supported by:
University Library of the Rijksuniversiteit Groningen
Univeristy Medical Center Groningen

Front cover: This thesis features the role of extrinsic cues (as depicted by branching tree for
vascular niche, soil for endosteal niche, different elements for cytokines, chemokines, growth
factors, etc.) and intrinsic cues (as depicted by colour gradient around red and green circles)
affecting BCR-ABL stem/progenitor cells (as indicated by red and green circles) for mediating
leukemogenesis.

Cover design: Painted by Keta Ladsaongikar
Printed by: CPI - KONINKLIJKE WÖHRMANN B.V., Zutphen

ISBN: 978-90-367-9015-4 (printed)
ISBN: 978-90-367-9014-7 (e-book)

© 2016 Pallavi S Sontakke
All rights reserved. No parts of this book may be reproduced or transmitted in any from or by any
means without prior permission of the author.

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Extrinsic and intrinsic cues involved in
BCR-ABL induced leukemogenesis

Establishing an ectopic humanized niche xenograft model and the study of
metabolic alterations in chronic myeloid leukemia

PhD thesis

to obtain the degree of PhD at the
University of Groningen
on the authority of the
Rector Magnificus Prof. E. Sterken
and in accordance with
the decision by the College of Deans.
This thesis will be defended in public on
Wednesday 28 September 2016 at 16:15 hours

by

Pallavi Suhas Sontakke
born on 29 September 1987
in Bhopal, India
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Supervisors

Prof. J.J. Schuringa
Prof. E. Vellenga

Assessment Committee

Prof. S. de Jong
Prof. J.H.M. van den Berg
Prof. G. Ossenkoppele

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DEDICATION

To my parents and my family for all their love, trust and support. I appreciate all their sacrifices and
I would not have been able to get this far without them.

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Paranimfen:

Susan Hilgendorf
Jennifer Jaques

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TABLE OF CONTENTS
Chapter 1 General introduction and scope of the thesis 9

Chapter 2 Modeling of chronic myeloid leukemia: an overview of in vivo murine
and human xenograft models.
Stem Cell International 2016 33

Chapter 3 Human BCR-ABL positive LSCs induce lymphoid and myeloid leukemia in a
human bone marrow-like scaffold-based xenograft model.
Leukemia 2016 59

Chapter 4 Hypoxia-like signatures induced by BCR-ABL potentially alter the glutamine
uptake for maintaining oxidative phosphorylation.
Plos One 2016 93

Chapter 5 Summary, discussion and future perspectives 117

Chapter 6 Nederlandse samenvatting 133
Acknowledgements 141

List of publications 147

Curriculum Vitae 148

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8
1
CHAPTER

General introduction and scope of the thesis

9