Etiology of Acute Leukemias in Children

332 Pages·2016·5.01 MB·English

by  Juan Manuel Mejía-Aranguré (eds.)

Etiology of
Acute Leukemias
in Children
Juan Manuel Mejía-Aranguré
Editor
123
Etiology of Acute Leukemias in Children

Juan Manuel Mejía-Aranguré
Editor
Etiology of Acute Leukemias
in Children
Editor
Juan Manuel Mejía-Aranguré
Coordinación de Investigación en Salud
Instituto Mexicano del Seguro Social
Ciudad de México
México
ISBN 978-3-319-05797-2 ISBN 978-3-319-05798-9 (eBook)
DOI 10.1007/978-3-319-05798-9
Library of Congress Control Number: 2016935716
Springer Cham Heidelberg New York Dordrecht London
© Springer International Publishing Switzerland 2016
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Pref ace
L eukemias cause the greatest number of deaths of children in the developed world
and some developing countries. Advances in the treatment of this disease laid the
foundation for much of what is known today about the treatment of cancer. In some
places in the world, survival rates of nearly 90 % have been attained for children
with leukemia. Despite these enormous achievements, not all countries have been
able to reach such survival rates for children with this disease. Even in countries
where cure of this illness is most probable, the anxiety that accompanies a diagnosis
of leukemia in the family and the suffering provoked by this disease underscore the
great necessity of seeking measures to prevent this disease. However, it is diffi cult
to prevent something when little is known about how and why it occurs. Nevertheless,
in the history of medicine there have been examples showing that, despite not
knowing with precision the cause of a disease, the fact of having a “theory” or a
theoretical model that supposes the causes leading to the occurrence of that disease
can lead to prevention of the illness. Such was the case of cholera in London in the
time of John Snow (1813–1858). In the mid-nineteenth century the cause of cholera
was not known, but Snow’s theoretical model of the pattern of outbreak of the
disease permitted him to postulate measures to end the outbreak.
The objective of this book is to expand a little more on what is known about the
origin of childhood leukemias. Although this volume contains some theoretical
aspects concerning the origin of childhood leukemia, the major portion of the con-
tent focuses on the different aspects that permit us to understand how leukemia
originates in children. First, a series of defi nitions is presented, followed by a dis-
cussion of the different environmental considerations that have been proposed and
studied as contributing factors in the development of leukemia. In addition to the
factors associated with the development of leukemia, another aspect, time, is con-
sidered as a variable—a window of vulnerability in a child’s life when environmen-
tal factors may more readily affect the child, thereby enabling the development of
the disease. Thereafter, an analysis of the possible role of some viruses in the devel-
opment of leukemia, most notably lymphocytic T-cell leukemia, is presented.
A later chapter describes one of the most interesting models aimed at
understanding childhood leukemia: the origin of leukemia in children with Down
v
vi Preface
syndrome. Myeloid and lymphoid leukemias in the child with Down syndrome have
presented the medical and research community with a great opportunity for
understanding how this disease develops. Further chapters deal with other interesting
topics, such as the molecular origin of lymphoid leukemias in children, and how a
niche in the bone marrow can contribute to the development of leukemia. Lastly a
theoretical model is presented, which attempts to integrate all the aspects described
in the preceding chapters, thereby allowing researchers to understand more about
how acute leukemia begins in children and, as a result, to begin to visualize possible
strategies for the prevention of this type of cancer.
This book is the commencement of a vast project—trying to understand the etiol-
ogy of acute leukemias in children. The authors do not pretend that the ideas con-
tained this book describe the manner in which leukemia originates; rather, the
authors present data, ideas, and theories that may serve as starting points from
which investigators will be able to further the understanding of how the factors
involved in this disease interact.
In the continuing study of the causes and origin of leukemias in children, I think
it imperative that the research be conducted in a more integrated manner, such that
advances made in the various disciplines are woven together to achieve a better
understanding of, and possibly the development of an integrated theory for,
leukemias in children. For the epidemiologist, molecular biologist, cellular biologist,
and those pediatricians and hematologists interested in the origins of childhood
leukemia, this book will provide a general vision of this disease from the point of
view of researchers who have been working in this fi eld. The readers will be the best
critics and a major stimulus for a reinvigoration of these research efforts, such that
more theories on leukemias in children may be combined, thus producing a broader
panorama of the origin of this illness in children.
México, D.F., Mexico Juan Manuel Mejía-Aranguré
Acknowledgments
T o each one of my collaborators who gave of their time and expertise, I extend my
sincere and profound thanks and gratefully acknowledge the enormous effort that
each one, despite facing full agendas, expended on this book. This volume is the
result of the commitment of researchers who realize that their principal function is
to divulge new fi ndings, instead of solely concentrating on their fi ndings, or
meditating on the current state of research and where it is heading. I feel very
fortunate to be the editor of a book that has such distinguished researchers as
contributors. Some of these collaborators are close friends. For others, I have had
the opportunity to play a role in their formation as researchers, and it is an honor to
see them so involved in a theme that, for many, has represented a life’s work.
Likewise, I thank Veronica Yakoleff who plays an important role in my work, in that
she not only translates the original Spanish text into English, but also provides
counsel and suggestions that are vital to each manuscript. I also thank the effort of
Gabriel Pires for his continual reminders for the completion of this work. Twenty-
six years ago, I began my career of carrying out research on leukemias in children,
when my great friend and mentor Arturo Fajardo presented me with the opportunity
of working side by side with him in a study of leukemias. His passion for this fi eld
of research inspired me; his formation as a pediatrician helped me to feel for the
children who were ill and to understand the pain they suffered. I thank him
profoundly for all his support throughout the 26 years we have worked together.
I dedicate this book to my friends and colleagues at the Hospital de Pediatría del
Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social in
Mexico City and, most especially, to my close friend Roberto Bernáldez. Roberto
and I had planned to be coeditors for this book; unfortunately, an illness impeded his
ability to collaborate with me, and, regrettably, he died last year. Roberto taught me
how to involve myself in the clinics; he always made me feel a part of his group of
hematologists in my beloved hospital. For that I will be forever thankful.
Space does not permit a complete list of all individuals whose collaboration
helped to produce this book. Ours is an ongoing collaboration, as this is not a
completed work. I offer my sincere thanks to each of my colleagues and to each of
the hematologists and oncologists that participated in the Mexican Inter-institutional
vii
viii Acknowledgments
Group for Identifying the Causes in Children with Leukemia. Over the years, several
sponsors have supported us to develop these studies on leukemias. Special thanks
are due to each of these sponsors, most especially the Instituto Mexicano del Seguro
Social (IMSS) and the Consejo Nacional de Ciencia y Technología of Mexico
(CONACYT), to whom we promised that this book would be completed; to the
Agrupación Mexicana para el Estudio de la Hematología, the agency that provided
me with the opportunity to travel to gather information to complete some aspects of
this work; and to the Coordinación de Investigación en Salud del IMSS, which has
always supported me in developing my administrative functions, but, more
importantly, has always given me the opportunity to continue advancing my
activities as a researcher. I am enormously grateful to all these individuals and
agencies; without their support, this work would not have been possible.
U ndoubtedly, every success brings with it someone who must make sacrifi ces. In
this case, I thank my wife Norma and my son Yurián, as they are the loved ones who
pay for each achievement I attain through afternoons being occupied and weekends
spent reviewing material. However, when I tell them what we have achieved, I see
that they share the pleasure with me; they, too, feel proud of each goal, of each
achievement. I am happy that they are proud of me: at least in my little world, I am
a hero.
As I have said, this book is only a beginning, the fi rst in a series concerning all
aspects of childhood leukemia. I hope that in the future, more researchers will be
able to join in a common effort to integrate what is known to date about, or what are
thought to be, the causes of leukemia in children. Perhaps none of us will be able to
demonstrate or discover all that we researchers would like to know about leukemia
in children, but the sharing and discussion of our “theories” may serve as a
springboard to both present and future investigators, thus leading to a better
understanding of the etiology of childhood leukemia. I am sure many researchers
share the hope that our legacy to others will be that, by passing on our knowledge
and discoveries to the next generation of researchers, the day when childhood
leukemia can be prevented will no longer be a dream.
I continue to pray to God that He guide us in this career path to prevent leukemia
in children. Although today we understand much concerning leukemias and our
fi ndings are published in the best peer-reviewed journals in the world, I caution
researchers that, while even one child still dies from this disease, we should consider
our efforts incomplete. Only God can give us the insight, the wisdom, and the
understanding. Only He has the keys to life and death and, if He wishes, He will
give us the keys to open the path to greater understanding of the origin of leukemias
and the key that will close this chapter on death by childhood leukemia. With God’s
help, we can hope for a world without this disease.
Contents
1 Introduction: Childhood Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Aurora Medina-Sanson
2 Etiology and Prevention of Acute Leukemias in Children . . . . . . . . . 49
Juan Carlos Núñez-Enríquez , Janet Flores-Lujano ,
Vilma Carolina Bekker-Méndez ,
David Aldebarán Duarte-Rodríguez ,
and Juan Manuel Mejía-Aranguré
3 HTLV-1 as a Model for Identifying the Causes
of Human Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
José Arellano-Galindo , Luz María Rocha-Ramírez ,
Sergio Zavala-Vega , Elva Jiménez-Hernández ,
Juan Xicotencatl-Cortés , Sara Ochoa-Pérez ,
and Juan Manuel Mejía-Aranguré
4 Etiology of Leukemia in Children with Down Syndrome . . . . . . . . . . 89
Ana C. Xavier , Yubin Ge , and Jeffrey W. Taub
5 Origin of Leukemia in Children with Down Syndrome . . . . . . . . . . 109
Johann K. Hitzler
6 Model for the Origin of Acute Leukemias in Children:
Interaction of Three Factors—Susceptibility, Exposure,
and Window of Vulnerability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Juan Manuel Mejía-Aranguré
7 Molecular Origin of Childhood Acute
Lymphoblastic Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Esmé Waanders , Marjolijn C. J. Jongmans ,
and Charles G. Mullighan
ix