-
EDITED BY
A Victor Hoffbrand MA, DM, FRCP, FRCPath, FRCP (Edin), DSc,
FMedSciEmeritus Professor of Haematology at University College
London and Honorary Consultant Haematologist at the Royal Free
Hospital, London, UK
Daniel Catovsky MD, DSc (Med), FRCPath, FRCP, FMedSciEmeritus
Professor of Haematology, Institute of Cancer Research, Sutton,
Surrey, UK
Edward GD Tuddenham MD, FRCP, FRCPath, FMedSciProfessor of
Haemophilia at University College London and Director of the
Haemophilia Centre at Royal Free Hospital, London, UK
Anthony R Green PhD, FRCP, FRCPath, FMedSciProfessor of
Haemato-oncology, Department of Haematology and Cambridge Institute
for Medical Research, University of Cambridge; Honorary Consultant
at Addenbrookes Hospital, Cambridge, UK
Sixth edition
Postgraduate Haematology
A John Wiley & Sons, Ltd., Publication
-
Postgraduate Haematology
-
Companion website
This book has a companion website:
www.wiley.com/go/hoffbrand/postgraduate
with:
Figures and tables from the book for downloading Interactive
multiple-choice questions prepared by the authors
-
EDITED BY
A Victor Hoffbrand MA, DM, FRCP, FRCPath, FRCP (Edin), DSc,
FMedSciEmeritus Professor of Haematology at University College
London and Honorary Consultant Haematologist at the Royal Free
Hospital, London, UK
Daniel Catovsky MD, DSc (Med), FRCPath, FRCP, FMedSciEmeritus
Professor of Haematology, Institute of Cancer Research, Sutton,
Surrey, UK
Edward GD Tuddenham MD, FRCP, FRCPath, FMedSciProfessor of
Haemophilia at University College London and Director of the
Haemophilia Centre at Royal Free Hospital, London, UK
Anthony R Green PhD, FRCP, FRCPath, FMedSciProfessor of
Haemato-oncology, Department of Haematology and Cambridge Institute
for Medical Research, University of Cambridge; Honorary Consultant
at Addenbrookes Hospital, Cambridge, UK
Sixth edition
Postgraduate Haematology
A John Wiley & Sons, Ltd., Publication
-
This edition fi rst published 2011 2005 by Blackwell Publishing
Ltd
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Library of Congress Cataloging-in-Publication Data
Postgraduate haematology / edited by A. Victor Hoffbrand ... [et
al.]. 6th ed. p. ; cm. Includes bibliographical references and
index. ISBN 978-1-4051-9180-7 1. BloodDiseases. 2. Hematology. I.
Hoffbrand, A. V. [DNLM: 1. Blood. 2. Hematologic Diseases. WH 100
P857 2011] RC633.P67 2011 616.15dc22
2009046376
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www.wiley.com/wiley-blackwell
-
v
Contents
Contributors, vii
Preface to the sixth edition, xi
Preface to the fi rst edition, xii
1 Stem cells and haemopoiesis, 1 Elaine Dzierzak
2 Erythropoiesis, 12 Douglas R Higgs and William G Wood
3 Iron metabolism, iron defi ciency and disorders of haem
synthesis, 26
A Victor Hoffbrand, Chaim Hershko and Clara Camaschella
4 Iron overload, 47 Clara Camaschella and A Victor Hoffbrand
5 Megaloblastic anaemia, 61 A Victor Hoffbrand
6 Haemoglobin and the inherited disorders of globin synthesis,
83
Swee Lay Thein and David Rees
7 Sickle cell disease, 109 Ashutosh Lal and Elliott P
Vichinsky
8 Hereditary disorders of the red cell membrane, 126
Edward C Gordon-Smith and Narla Mohandas
9 Disorders of red cell metabolism, 140 Alberto Zanella and
Edward C Gordon-Smith
10 Acquired haemolytic anaemias, 158 Edward C Gordon-Smith and
Modupe O Elebute
11 Paroxysmal nocturnal haemoglobinuria, 176 Peter Hillmen
12 Inherited aplastic anaemia/bone marrow failure syndromes,
186
Inderjeet S Dokal
13 Acquired aplastic anaemia, 206 Judith CW Marsh and Neal S
Young
14 Red cell immunohaemotology: introduction, 226 Marcela
Contreras and Geoff Daniels
15 Antigens in human blood, 244 Marcela Contreras and Geoff
Daniels
16 Clinical blood transfusion, 268 Marcela Contreras, Clare PF
Taylor and
John A Barbara
17 Phagocytes, 300 John Mascarenhas, Farhad Ravandi and
Ronald Hoffman
18 Lysosomal storage disorders, 330 Atul B Mehta and Derralynn A
Hughes
19 Normal lymphocytes and non-neoplastic lymphocyte disorders,
343
Paul AH Moss and Mark T Drayson
20 The spleen, 368 Paul AH Moss
21 The molecular basis of leukaemia and lymphoma, 380 George S
Vassiliou and Anthony R Green
22 Laboratory diagnosis of haematological neoplasms, 395
Barbara J Bain and Torsten Haferlach
23 Acute myeloid leukaemia, 415 Alan K Burnett and Adriano
Venditti
24 Adult acute lymphoblastic leukaemia, 433 Nicola Gkbuget and
Dieter Hoelzer
25 Childhood acute lymphoblastic leukaemia, 448 Dario Campana
and Ching-Hon Pui
26 Supportive care in the management of leukaemia, 463
Archibald G Prentice and J Peter Donnelly
27 Chronic myeloid leukaemia, 483 John M Goldman and Tariq I
Mughal
28 The myelodysplastic syndromes, 503 Timothy JT Chevassut and
Ghulam J Mufti
-
Contents
vi
29 Chronic lymphocytic leukaemia and other B-cell disorders,
530
Daniel Catovsky and Emili Montserrat
30 T-cell lymphoproliferative disorders, 558 Estella Matutes
31 Multiple myeloma, 577 Jess San-Miguel and Joan Blad
32 Amyloidosis, 599 Simon DJ Gibbs and Philip N Hawkins
33 The classifi cation of lymphoma: updating the WHO classifi
cation, 614
Elias Campo and Stefano A Pileri
34 Hodgkin lymphoma, 639 Jonathan Sive and David Linch
35 Non-Hodgkin lymphoma, 655 Kate Cywnarski and Anthony H
Goldstone
36 Myeloproliferative neoplasms, 686 Peter J Campbell and
Anthony R Green
37 Histocompatibility, 710 Ann-Margaret Little, Steven GE Marsh
and
J Alejandro Madrigal
38 Stem cell transplantation, 722 Charles Craddock and Ronjon
Chakraverty
39 Normal haemostasis, 746 Keith Gomez, Edward GD Tuddenham
and
John H McVey
40 The vascular function of platelets, 772 Stephen P Watson and
Paul Harrison
41 Inherited bleeding disorders, 793 Michael A Laffan and K John
Pasi
42 Rare bleeding disorders, 813 Flora Peyvandi and Marzia
Menegatti
43 Acquired coagulation disorders, 839 Peter W Collins, Jecko
Thachil and Cheng-Hock Toh
44 Thrombotic thrombocytopenic purpura and haemolyticuraemic
syndrome (congenital and acquired), 860
Pier M Mannucci, Flora Peyvandi and Roberta Palla
45 Heritable thrombophilia, 872 Trevor Baglin
46 Acquired venous thrombosis, 888 Beverley J Hunt and Michael
Greaves
47 Management of venous thromboembolism, 900 Beverly J Hunt
48 Congenital platelet disorders, 915 Maurizio Margaglione and
Paul RJ Ames
49 Primary immune thrombocytopenia, 928 Drew Provan and Adrian C
Newland
50 Haematological aspects of systemic disease, 940 Atul B Mehta
and A Victor Hoffbrand
51 Haematological aspects of tropical diseases, 956 Imelda Bates
and Ivy Ekem
52 Neonatal haematology, 971 Irene AG Roberts
Appendix I Normal values, 985
Appendix II World Health Organization classifi cation of tumours
of the haematopoietic and lymphoid tissues, 986
Index, 989
www.wiley.com/go/hoffbrand/postgraduate
Companion website
This book has a companion website:
www.wiley.com/go/hoffbrand/postgraduate
with:
Figures and tables from the book for downloading Interactive
multiple-choice questions prepared by the authors
-
vii
Contributors
Paul RJ Ames Consultant Haematologist Department of Haematology
Airedale General Hospital Steeton UK
Trevor Baglin Consultant Haematologist Department of Haematology
Cambridge University Hospitals NHS Trust Addenbrookes Hospital
Cambridge UK
Barbara J Bain Department of Haematology St Mary s Hospital
London UK
John A Barbara Emeritus Microbiology Consultant NHS Blood and
Transplant Colindale London UK
Imelda Bates Reader in Tropical Haematology Liverpool School of
Tropical Medicine Liverpool UK
Joan Blad Senior Consultant Haematologist Servicio de Hematolog
a Hospital Clinic de Barcelona Barcelona Spain
Alan K Burnett Department of Haematology School of Medicine
Cardiff University Cardiff UK
Clara Camaschella Professor of Medicine Vita - Salut University;
Division of Genetics and Cell Biology San Raffaele Scientifi c
Institute Milan Italy
Dario Campana Vice Chair for Laboratory Research Departments of
Oncology and Pathology St Jude Children s Research Hospital
Memphis, TN USA
Peter J Campbell Cancer Genome Project Wellcome Trust Sanger
Institute Cambridge UK
Elias Campo Clinical Director and Professor of Pathology Center
for Biomedical Diagnosis and Chief of
Hematopathology Unit Hospital Clinic University of Barcelona
Barcelona Spain
Daniel Catovsky Emeritus Professor of Haematology Institute of
Cancer Research Sutton Surrey UK
Ronjon Chakraverty Royal Free and University College Medical
School London UK
Timothy JT Chevassut Senior Lecturer and Honorary Consultant
in
Haematology Brighton and Sussex Medical School Royal Sussex
County Hospital Brighton UK
Peter W Collins Senior Lecturer in Haematology Department of
Haematology School of Medicine Cardiff University University
Hospital of Wales Cardiff UK
Marcela Contreras University College London and Blood
Transfusion
International London UK
Charles Craddock Centre for Clinical Haematology Leukaemia Unit
Queen Elizabeth Hospital Birmingham UK
Kate Cwynarski Consultant Haematologist and Honorary Senior
Lecturer Department of Haematology Royal Free Hospital London
UK
Geoff Daniels Consultant Clinical Scientist Bristol Institute
for Transfusion Sciences NHS Blood and Transplant Bristol UK
-
Contributors
viii
Inderjeet S Dokal Chair of Paediatrics and Child Health Centre
Lead Barts and The London School of Medicine and
Dentistry Queen Mary University of London Barts and The London
Children s Hospital London UK
J Peter Donnelly Department of Haematology University Hospital
Nijmegen Nijmegen The Netherlands
Mark T Drayson Department of Immunology University of Birmingham
Medical School Birmingham UK
Elaine Dzierzak Department of Cell Biology Erasmus Stem Cell
Institute Erasmus Medical Centre Rotterdam The Netherlands
Ivy Ekem Senior Lecturer and Head Department of Haematology
University of Ghana Medical School Accra Ghana
Modupe O Elebute Consultant Haematologist King s College
Hospital London UK
Simon DJ Gibbs Clinical Academic Research Fellow (Haematology)
National Amyloidosis Centre University College London Medical
School; Royal Free Hospital London UK
Nicola G kbuget Head of Study Center Goethe University Hospital
Department of Medicine II Hematology/Oncology Frankfurt Germany
John M Goldman Department of Haematology Imperial College School
of Medicine Hammersmith Hospital London UK
Anthony H Goldstone Department of Haematology University College
London London UK
Keith Gomez Senior Lecturer in Haematology Haemophilia Centre
and Thrombosis Unit Royal Free and University College London
Medical School London UK
Edward C Gordon - Smith Department of Haematology St George s
Hospital Medical School London UK
Michael Greaves Professor of Haematology Head of School of
Medicine and Dentistry University of Aberdeen Aberdeen UK
Anthony R Green Department of Haematology University of
Cambridge Cambridge Institute for Medical Research Cambridge UK
Torsten Haferlach MLL Munich Leukemia Laboratory GmbH Munich
Germany
Paul Harrison Clinical Scientist Oxford Haemophilia and
Thrombosis Centre The Churchill Hospital Headington Oxford UK
Philip N Hawkins Clinical Director National Amyloidosis Centre
University College London Medical School Royal Free Hospital London
UK
Chaim Hershko Department of Medicine Shaare Zedek Medical
Centre; Professor Emeritus Hebrew U Hadassah Medical School
Jerusalem Israel
Douglas R Higgs Professor of Molecular Haematology MRC Molecular
Haematology Unit Weatherall Institute of Molecular Medicine John
Radcliffe Hospital Oxford UK
Peter Hillmen Department of Haematology St James s University
Hospital Leeds UK
Dieter Hoelzer Professor of Internal Medicine Onkologikum
Frankfurt Museum Embankment Frankfurt Germany
A Victor Hoffbrand Emeritus Professor of Haematology University
College Medical School; Honorary Consultant Haematologist Royal
Free Hospital London UK
Ronald Hoffman Albert A and Vera List Professor of Medicine
Tisch Cancer Institute Mount Sinai School of Medicine New York, NY
USA
Derralynn A Hughes Senior Lecturer in Haematology Department of
Academic Haematology Royal Free and University College Medical
School London UK
-
Contributors
ix
Beverley J Hunt Thrombosis and Haemostasis King s College; Guy s
and St Thomas NHS Foundation Trust London UK
Michael A Laffan Department of Haematology, Faculty of Medicine
Imperial College School of Medicine Hammersmith Hospital London
UK
Ashutosh Lal Hematology/Oncology Children s Hospital and
Research Center at
Oakland Oakland, CA USA
David Linch Department of Haematology UCL Medical School London
UK
Ann - Margaret Little Histocompatibility and Immunogenetics
Service Gartnavel General Hospital Glasgow UK
John H McVey Weston Professor of Molecular Medicine Molecular
Medicine Thrombosis Research Institute London UK
J Alejandro Madrigal The Anthony Nolan Research Institute Royal
Free Hospital London UK
Pier M Mannucci Professor and Chairman of Internal Medicine A.
Bianchi Bonomi Hemophilia and Thrombosis
Center IRCCS C Granada Maggiore Hospital Foundation; Department
of Internal Medicine University of Milan and Luigi Villa Foundation
Milan Italy
Maurizio Margaglione Associate Professor Medical Genetics
Department of Biomedical Sciences University of Foggia Foggia
Italy
Judith CW Marsh Department of Haematological Medicine King s
College Hospital London UK
Steven GE Marsh The Anthony Nolan Research Institute Royal Free
Hospital London UK
John Mascarenhas Assistant Professor of Medicine Division of
Hematology/Oncology Tisch Cancer Institute Mount Sinai School of
Medicine New York, NY USA
Estella Matutes Reader and Consultant Haematologist Royal
Marsden Hospital and Institute of Cancer
Research London UK
Atul B Mehta Consultant Haematologist Department of Haematology
University College London School of Medicine Royal Free Hospital
London UK
Marzia Menegatti A. Bianchi Bonomi Hemophilia and Thrombosis
Center IRCCS C Granada Maggiore Hospital Foundation; Department
of Internal Medicine University of Milan and Luigi Villa Foundation
Milan Italy
Narla Mohandas Vice President of Research New York Blood Center
New York, NY USA
Emili Montserrat Director, Institute of Hematology and Oncology
Hospital Clinic University of Barcelona Barcelona Spain
Paul AH Moss Professor of Haematology and Head of School of
Cancer Sciences University of Birmingham Birmingham UK
Ghulam J Mufti Head, Department of Haematological Medicine King
s College Hospital and Kings College London London UK
Tariq I Mughal Guy s Hospital London UK
Adrian C Newland Professor of Haematology Department of
Haematology Queen Mary University of London London UK
Roberta Palla A. Bianchi Bonomi Hemophilia and Thrombosis
Center IRCCS C Granada Maggiore Hospital Foundation; Department
of Internal Medicine University of Milan and Luigi Villa Foundation
Milan Italy
K John Pasi Centre for Haematology Institute of Cell and
Molecular Science Barts and The London School of Medicine and
Dentistry London UK
Flora Peyvandi Associate Professor of Internal Medicine A.
Bianchi Bonomi Hemophilia and Thrombosis
Center IRCCS C Granada Maggiore Hospital Foundation; Department
of Internal Medicine University of Milan and Luigi Villa Foundation
Milan Italy
-
Contributors
x
Stefano A Pileri Professor of Pathology Department of
Haematology and Oncological
Sciences; Director of the Haematopathology Unit Bologna
University School of Medicine St Orsola Hospital Bologna Italy
Archibald G Prentice Department of Haematology Royal Free
Hospital London UK
Drew Provan Senior Lecturer in Haematology Department of
Haematology Queen Mary University of London London UK
Ching - Hon Pui Departments of Oncology and Pathology St Jude
Children s Research Hospital Memphis, TN USA
Farhad Ravandi Department of Leukaemia University of Texas MD
Anderson Cancer Center Houston, TX USA
David Rees Senior Lecturer King s College Hospital; Consultant
Paediatric Haematologist Department of Haematological Medicine King
s College London School of Medicine London UK
Irene AG Roberts Professor of Paediatric Haematology Centre for
Haematology Hammersmith Campus Imperial College London London
UK
Jes s San - Miguel Professor and Chairman of Haematology
Department of Haematology Hospital Universitario de Salamanca
Salamanca Spain
Jonathan Sive Department of Haematology UCM Medical School
London UK
Clare PF Taylor Medical Director of SHOT Medical Directorate
North London Blood Centre London UK
Jecko Thachil Clinical Research Fellow in Haematology School of
Clinical Sciences University of Liverpool Liverpool UK
Swee Lay Thein Professor of Molecular Haematology Department of
Haematological Medicine King s College Hospital; Consultant
Haematologist Division of Gene and Cell Based Therapy King s
College London School of Medicine London UK
Cheng - Hock Toh Professor of Haematology School of Clinical
Sciences University of Liverpool Liverpool UK
Edward GD Tuddenham Katharine Dormandy Chair of Haemophilia
Haemophilia Centre and Thrombosis Unit Royal Free and University
College London
Medical School London UK
George Vassiliou Wellcome Trust Sanger Institute Wellcome Trust
Genome Campus Cambridge UK
Adriano Venditti Associate Professor Department of Haematology
Policlinico Tor Vergata Rome Italy
Elliott P Vichinsky Hematology/Oncology Children s Hospital and
Research Center at
Oakland Oakland, CA USA
Stephen P Watson BHF Chair in Cardiovascular Sceinces and
Cellular Pharmacology Division of Medical Sciences Institute of
Biomedical Research Centre for Cardiovascular Sciences University
of Birmingham Birmingham UK
William G Wood Professor in Haematology Weatherall Institute of
Molecular Medicine John Radcliffe Hospital Oxford UK
Neal S Young National Heart, Lung, and Blood Institute National
Institutes of Health Bethesda, MD USA
Alberto Zanella Hematology 2 Unit IRCCS C Granada Maggiore
Hospital Foundation Milan Italy
-
xi
Preface to the s ixth e dition
Haematology continues to advance and change more rapidly than
most areas of medicine. This sixth edition of Postgraduate
Haematology includes much knowledge that has been gained in the fi
ve years since the previous edition. Professor Tony Green of the
Department of Haematology, University of Cambridge has joined the
editors of the last edition to help cover malignant diseases, where
major changes have occurred in their classifi ca-tion (WHO, 2008)
and in diagnostic procedures and treatment protocols.
Haematological oncology now forms the major workload for many
consultant haematologists. Nevertheless, benign conditions are a
major source of work for the general haematologist and chapters
concerning all these conditions have been extensively updated,
often by new authors.
Despite increased understanding of the molecular basis of
haematological diseases and advances in their investigation and
management, we have kept the size of the book unchanged by omitting
ten chapters from the fi fth edition and incorporating their
essential information into the remaining chapters.
As for previous editions, this book is aimed at providing
haematologists in training and consultants with up - to - date
knowledge of the aetiology of blood diseases combined with a
practical guide to their investigation and treatment. The views
expressed are those of the individual authors but relevant
litera-ture is listed at the end of each chapter to provide
additional reference material.
Many of our authors are based outside the UK, particularly in
Europe and the USA, and we hope this book will be used by
haematologists practising in the UK, Europe and internation-ally.
We are grateful to our publishers Wiley - Blackwell for their
unstinting help during the publishing process and particularly to
Rebecca Huxley and Jennifer Seward. We also thank Jane Fallows who,
as previously, has with great expertise drawn all the scientifi c
diagrams.
London and Cambridge, 2011 AVH, DC, EGDT, ARG
-
xii
Preface to the fi rst e dition
In this book the authors combine an account of the
physiologi-cal and biochemical basis of haematological processes
with descriptions of the clinical and laboratory features and
manage-ment of blood disorders. Within this framework, each author
has dealt with the individual subjects as he or she thought
appropriate. Because this book is intended to provide a founda-tion
for the study of haematology and is not intended to be a reference
book, it refl ects, to some extent, the views of the individual
authors rather than providing comprehensive detail and a full
bibliography. For these the reader is referred to the selected
reading given at the end of each chapter. It is hoped that the book
will prove of particular value to students taking either the
Primary or the Final Part of the examination for Membership of the
Royal College of Pathologists and the Diplomas of Clinical
Pathology. It should also prove useful to physicians wishing to
gain special knowledge of haematology and to technicians taking the
Advanced Diploma in Haematology of the Institute of Medical
Laboratory Technology, or the Higher National Certifi cate in
Medical Laboratory subjects.
We wish to acknowledge kind permission from the editors and
publishers of the British Journal of Haematology , the Journal
of the Royal College of Physicians of London and the Quarterly
Journal of Medicine for permission to reproduce fi gures 4.1, 4.5,
4.10, 4.11, 4.12, 9.4 and 9.10, also the publishers of Progress in
Haematology for fi gure 7.2, and many other publishers who,
together with the authors, have been acknowledged in the text. We
are particularly grateful to Professor J.V. Dacie for provid-ing
material which formed the basis of many of the original
illustrations in Chapters 4 8 . We are greatly indebted to Mrs T.
Charalambos, Mrs J. Cope and Mrs D. Haysome for secretarial
assistance and to Mrs P. Schilling and the Department of Medical
Illustration for photomicrography, art work and general
photography.
Finally, we are grateful for the invaluable help and
forbear-ance we have received from Mr R. Emery and William
Heinemann Medical Books.
London, 1972 AVH SML
-
1
Postgraduate Haematology : 6th edition. Edited by A. Victor
Hoffbrand, Daniel Catovsky, Edward G.D. Tuddenham, Anthony R. Green
2011 Blackwell Publishing Ltd.
CHAPTER 1
Stem c ells and h aemopoiesis Elaine Dzierzak Erasmus Stem Cell
Institute, Erasmus Medical Centre, Rotterdam, The Netherlands
1
Introduction , 1 Hierarchical organization and lineage
relationships in the adult haemopoietic system , 1
Sites of adult haemopoiesis , 3 Development of HSCs , 3 Waves of
haemopoietic generation in embryonic
development, 3
Embryonic haemopoietic sites and haemopoietic migration, 5
HSC quiescence, proliferation and ageing, 6 Haemopoietic
supportive
microenvironments , 6 Adult bone marrow microenvironment, 6
Microenvironments important for haemopoietic
development in the conceptus, 7
Haemopoietic regenerative and replacement therapies , 8
Stem cell transplantation, 8 New sources of HSCs for
transplantation, 8 Selected bibliography , 10
Introduction
Haemopoietic stem cells (HSCs) are the foundation of the adult
blood system and sustain the lifelong production of all blood
lineages. These rare cells are generally defi ned by their ability
to self - renew through a process of asymmetric cell division, the
outcome of which is an identical HSC and a differentiating cell.
Through a series of proliferation and differentiation events,
mature blood cells are produced. In health, HSCs provide
homeostatic maintenance of the system through their ability to
generate the hundreds of millions of erythrocytes and leuco-cytes
needed each day. In trauma and physiological stress, HSCs are
triggered to replace the lost or damaged blood cells. The tight
regulation of HSC self - renewal ensures the appropriate balance of
blood cell production. Perturbation of this regula-tion and
unchecked growth of HSCs and/or immature blood cells results in
leukaemia. Over the last 50 years, bone marrow transplantation, and
more recently cord blood transplantation, have underscored the
medical value of stem cell regenerative therapy. However, insuffi
cient numbers of HSCs are still a major constraint in clinical
applications. As the pivotal cells in this essential tissue, HSCs
are the focus of intense research to further our understanding of
their normal behaviour and the basis of their dysfunction in
haemopoietic disease and leukae-mia, and to provide insights and
new strategies into improved clinical transplantation therapies.
This chapter provides current and historical information on the
organization of the adult haemopoietic cell differentiation
hierarchy, the ontogeny of HSCs, the stromal microenvironment
supporting these cells,
and the molecular mechanisms involved in the regulation of
HSCs.
Hierarchical o rganization and l ineage r elationships in the a
dult h aemopoietic s ystem
The haemopoietic system is the best - characterized cell lineage
differentiation hierarchy and, as such, has set the paradigm for
the growth and differentiation of tissue - specifi c stem cells
(Table 1.1 ). HSCs are defi ned by their high proliferative
poten-tial, ability to self - renew and potential to give rise to
all haemo-poietic lineages. HSCs produce immature progenitors that
gradually and progressively, through a series of proliferation and
differentiation events, become restricted in lineage
differ-entiation potential. Such restricted progenitors produce the
terminally differentiated functional blood cells.
The lineage relationships of the variety of cells within the
adult haemopoietic hierarchy (Figure 1.1 ) are based on results of
in vivo transplantation assays in radiation chimeric mice and many
in vitro differentiation assays that became available following the
identifi cation of haemopoietic growth factors. These assays
facilitated measurement of the maturational pro-gression of stem
cells and progenitors, at or near the branch points of lineage
commitment. Clonal analyses, in the form of colony - forming unit
(CFU) assays, were developed to defi ne the lineage differentiation
potential of the stem cell or progenitor, and to quantitate the
number/frequency of such cells in the population as a whole. In
general, the rarer a progenitor is and the greater its lineage
differentiation potential, the closer it is in the hierarchy to the
HSC. In vitro clonogenic assays measure the most immature
progenitor CFU - GEMM/Mix (granulocyte, erythroid, macrophage,
megakaryocyte), bipotent progenitors
Postgraduate Haematology, Sixth
editionContentsContributorsPreface to the sixth editionPreface to
the first editionCHAPTER 1: Stem cells and haemopoiesisCHAPTER 2:
ErythropoiesisCHAPTER 3: Iron metabolism, iron deficiency and
disorders of haem synthesisCHAPTER 4: Iron overloadCHAPTER 5:
Megaloblastic anaemiaCHAPTER 6: Haemoglobin and the inherited
disorders of globin synthesisCHAPTER 7: Sickle cell diseaseCHAPTER
8: Hereditary disorders of the red cell membraneCHAPTER 9:
Disorders of red cell metabolismCHAPTER 10: Acquired haemolytic
anaemiasCHAPTER 11: Paroxysmal nocturnal haemoglobinuriaCHAPTER 12:
Inherited aplastic anaemia/bone marrow failure syndromesCHAPTER 13:
Acquired aplastic anaemiaCHAPTER 14: Red cell immunohaematology:
introductionCHAPTER 15: Antigens in human bloodCHAPTER 16: Clinical
blood transfusionCHAPTER 17: PhagocytesCHAPTER 18: Lysosomal
storage disordersCHAPTER 19: Normal lymphocytes and non-neoplastic
lymphocyte disordersCHAPTER 20: The spleenCHAPTER 21: The molecular
basis of leukaemia and lymphomaCHAPTER 22: Laboratory diagnosis of
haematological neoplasmsCHAPTER 23: Acute myeloid leukaemiaCHAPTER
24: Adult acute lymphoblastic leukaemiaCHAPTER 25: Childhood acute
lymphoblastic leukaemiaCHAPTER 26: Supportive care in the
management of leukaemiaCHAPTER 27: Chronic myeloid leukaemiaCHAPTER
28: The myelodysplastic syndromesCHAPTER 29: Chronic lymphocytic
leukaemia and other B-cell disordersCHAPTER 30: T-cell
lymphoproliferative disordersCHAPTER 31: Multiple myelomaCHAPTER
32: AmyloidosisCHAPTER 33: The classification of lymphomas:
updating the WHO classificationCHAPTER 34: Hodgkin lymphomaCHAPTER
35: Non-Hodgkin lymphomaCHAPTER 36: Myeloproliferative
neoplasmsCHAPTER 37: HistocompatibilityCHAPTER 38: Stem cell
transplantationCHAPTER 39: Normal haemostasisCHAPTER 40: The
vascular function of plateletsCHAPTER 41: Inherited bleeding
disordersCHAPTER 42: Rare bleeding disordersCHAPTER 43: Acquired
coagulation disordersCHAPTER 44: Thrombotic thrombocytopenic
purpura and haemolyticuraemic syndrome (congenital and
acquired)CHAPTER 45: Heritable thrombophiliaCHAPTER 46: Acquired
venous thrombosisCHAPTER 47: Management of venous
thromboembolismCHAPTER 48: Congenital platelet disordersCHAPTER 49:
Primary immune thrombocytopeniaCHAPTER 50: Haematological aspects
of systemic diseaseCHAPTER 51: Haematological aspects of tropical
diseasesCHAPTER 52: Neonatal haematologyAPPENDIX 1: Normal
valuesAPPENDIX 2: World Health Organization classification of
tumours of the haematopoietic and lymphoid tissuesIndex