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Molecular Hematology
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Molecular
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Hematology
FIFTH EDITION
Edited by
Drew Provan
Hillard M. Lazarus

This edition first published 2024
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© 2024 by John Wiley & Sons Ltd
Edition History [4th edition, 2020]
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise,
except as permitted by law. Advice on how to obtain permission to reuse material from this title is
available at http://www.wiley.com/go/permissions.
The right of Drew Provan and Hillard M. Lazarus to be identified as the author(s) of the editorial
material in this work has been asserted in accordance with law.
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John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
For details of our global editorial offices, customer services, and more information about Wiley
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Inc. and/or its affiliates in the United States and other countries and may not be used without written
permission. All other trademarks are the property of their respective owners. John Wiley & Sons, Inc.
is not associated with any product or vendor mentioned in this book.
Limit of Liability/Disclaimer of Warranty
The contents of this work are intended to further general scientific research, understanding, and
discussion only and are not intended and should not be relied upon as recommending or promoting
scientific method, diagnosis, or treatment by physicians for any particular patient. In view of ongoing
research, equipment modifications, changes in governmental regulations, and the constant flow of
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evaluate the information provided in the package insert or instructions for each medicine, equipment,
or device for, among other things, any changes in the instructions or indication of usage and for added
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this work, they make no representations or warranties with respect to the accuracy or completeness of
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This work is sold with the understanding that the publisher is not engaged in rendering professional
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Neither the publisher nor authors shall be liable for any loss of profit or any other commercial
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on- demand. Some
Library of Congress Cataloging- in- Publication Data
Names: Provan, Drew, 1955– editor. | Lazarus, Hillard M., editor.
Title: Molecular hematology / edited by Drew Provan, Hillard M. Lazarus.
Description: Fifth edition. | Hoboken, NJ : Wiley-Blackwell, 2024. |
Includes bibliographical references and index.
Identifiers: LCCN 2023049669 (print) | LCCN 2023049670 (ebook) | ISBN
9781394180455 (cloth) | ISBN 9781394180462 (Adobe PDF) | ISBN
9781394180479 (epub) | ISBN 9781394180486 (obook)
Subjects: MESH: Hematologic Diseases | Molecular Biology–methods
Classification: LCC RC636 (print) | LCC RC636 (ebook) | NLM WH 120 | DDC
616.1/5–dc23/eng/20240102
LC record available at https://lccn.loc.gov/2023049669
LC ebook record available at https://lccn.loc.gov/2023049670
Cover Image: © JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty Images
Cover Design by Wiley
Set in 10/12pt MinionPro by Straive, Pondicherry, India

Dedication
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From Dr. Lazarus:
To my family: Joan, the love of my life, our two sons, their wives, and our grandchildren.
From Dr. Provan:
To my son, Fraser, for providing constant guitar inspiration and for bringing me joy.

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Contents
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List ofcontributors, ix
Foreword, xiii
Preface, xv
1 Beginnings: themolecular pathology ofhemoglobin, 1
Douglas Higgs and Mohsin Badat
2 Stem cells, 17
David T. Scadden
3 The genetics ofacute myeloidleukemia, 33
Amye M. Harrigan and Amy M. Trottier
4 Molecular diagnostics andrisk assessment inmyeloid
malignancies, 51
Christian Scharenberg and Torsten Haferlach
5 Molecular basis ofacute lymphoblastic leukemia, 67
Shunsuke Kimura and Charles G. Mullighan
6 Chronic myelogenous leukemia, 83
Hagop Kantarjian, Elias Jabbour and Susan O’Brien
7 Myeloproliferative neoplasms, 99
Jessica Spiers, Dina Mahdi, Christopher Saunders and
Donal P. McLornan
8 Lymphoma genetics, 113
Giovanni Insuasti- Beltran, Chad M. McCall and
EricD.Hsi
13 Molecular basis ofiron metabolism, 175
Jodie L. Babitt and Tomas Ganz
14 Perspectives ingenomics andsickle cell disease
therapeutics, 187
Ambroise Wonkam
15 Molecular coagulation andthrombophilia, 201
Björn Dahlbäck and Andreas Hillarp
16 The molecular basis ofhemophilia, 217
Keith Gomez
17 The molecular basis ofvon Willebrand disease, 231
Omid Seidizadeh and Luciano Baronciani
18 Platelet disorders, 251
Kenneth J. Clemetson
19 The molecular basis ofblood cell alloantigens, 267
Winnie Chong, Louise Tilley and Colin Brown
20 Functions ofblood group antigens, 285
Jonathan S. Stamler, Marilyn J. Telen and Carla Dinardo
21 Autoimmune hematological disorders, 299
Drew Provan and John W. Semple
22 Molecular therapeutics inhematology: gene
therapy, 321
William M. McKillop and Jeffrey A. Medin
23 Pharmacogenomics, 343
Leo Kager and William E. Evans
9 Molecular basis ofchronic lymphocytic leukemia, 127
Bita Fakhri and Alexey Danilov
10 The molecular biology of multiplemyeloma, 137
Udit Yadav and Wilson I. Gonsalves
11 The molecular basis ofbone marrow failure syndromes
andred cell enzymopathies, 145
Deena Iskander, Lucio Luzzatto and
AnastasiosKaradimitris
12 Anemia ofchronic disease, 169
Tomas Ganz and Elizabeta Nemeth
24 Cancer stem cells, 359
Sara Ali and Dominique Bonnet
25 CAR- T cell therapy, 369
Jude Franklin, Prateek Pophali, Zachary Jackson,
David Wald and David Avigan
26 Molecular basis oftransplantation, 397
Pramila Krishnamurthy, Victoria Potter and
FrancescoDazzi
Index 413

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