Molecular Hematology 5th Edition by Drew Provan, Hillard Lazarus 1394180454 9781394180455

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ISBN 10: 1394180454

ISBN 13: 9781394180455

Author: Drew Provan, Hillard M. Lazarus

Molecular Hematology brings together the most up-to-date and reliable information on the molecular basis of major hematologic diseases. Edited and authored by leading experts in the field, this volume demonstrates the clinical relevance of molecular biology in the diagnosis and treatment of blood disorders. Concise, accessible chapters address key topics in modern hematology, such as lymphoma genetics, molecular coagulation, thrombophilia, pharmacogenomics, platelet disorders, hemophilia, anemia, and multiple myeloma. Chapters introduce and summarize specific hematologic diseases, explore the pathogenesis of the disorder, highlight new and emerging molecular strategies, and more.

Now in its fifth edition, Molecular Hematology is fully revised to incorporate contemporary hematology research and practice. Entirely new chapters cover topics such as CAR-T cell technology, COVID, cancer cell biology, gene therapy and gene editing in clinical practice, as well as the impact of molecular research on the diagnosis and treatment of various malignant hematologic diseases. This edition includes updated suggested readings and a wealth of new full-color charts, graphs, and illustrations throughout.

• Covers the molecular biology of different blood diseases, their pathogeneses, and current molecular research and therapies
• Illustrates the impact of molecular research on hematologic investigations and therapeutics
• Discusses how progress in basic science and therapeutics has improved the diagnosis and care of patients with various hematologic disorders
• Surveys recent developments in cancer-cell biology, with an emphasis on leukemia and lymphoma
• Includes access to a companion Digital Edition providing search across the book, downloadable illustrations, and notation tools

Molecular Hematology is a must-have resource for established and trainee clinicians, clinical scientists and researchers, medical students, and upper-level undergraduates in the fields of hematology, oncology, and molecular biology.

Molecular Hematology 5th Table of contents:

Chapter 1: Beginnings: the molecular pathology of hemoglobin
Introduction
Normal structure and function of hemoglobin and the globin genes
Molecular pathology of the globin genes
The pathophysiology and clinical phenotypes of thalassemia
Conclusion
Further reading

Chapter 2: Stem cells
Introduction
Stem cell definitions and distinctions
Hematopoietic stem cell concepts and their origin
Molecular regulation of hematopoiesis
Trafficking of primitive hematopoietic cells
Manipulating hematopoietic stem cells for clinical use
Summary
Further reading

Chapter 3: The genetics of acute myeloid leukemia
Introduction
AML with recurrent cytogenetic abnormalities
Molecular genetic aberrations not detectable by conventional cytogenetics
Activated signaling
Myeloid transcription factors
Tumor suppressors
Spliceosome genes
Cohesin complex gene
DNA methylation
Chromatin modifiers
Germline predisposition
AML therapies and MRD monitoring targeted by genetics
Summary
Further reading

Chapter 4: Molecular diagnostics and risk assessment in myeloid malignancies
Introduction
Methods of detection
Karyotypic evolution
Clinical implications
Treatment selection
Therapy‐related chromosomal aberrations in AML post cytotoxic therapy
Mutations in splicing factors
Epigenetic regulators
Histone modification
DNA methylation
Cohesin complex
Transcription factors
Cell signaling genes
References
Further reading

Chapter 5: Molecular basis of acute lymphoblastic leukemia
Introduction
B‐cell precursor acute lymphoblastic leukemia
High hyperdiploid ALL
Hypodiploid ALL
Intrachromosomal amplification of chromosome 21 (iAMP21)
ETV6::RUNX1 and ETV6::RUNX1‐like ALL
TCF3‐rearranged ALL (TCF3::PBX1 and TCF3::HLF)
KMT2A‐rearranged ALL
BCR::ABL1 (Ph+) and Ph‐like ALL
DUX4‐rearranged ALL
MEF2D‐rearranged ALL
ZNF384‐rearranged leukemia
PAX5‐driven ALL (PAX5alt and PAX5 P80R)
CDX2/UBTF ALL
NUTM1‐rearranged ALL
IKZF1 N159Y
Other subtypes of B‐ALL
T‐cell precursor acute lymphoblastic leukemia (T‐ALL)
TLX1 and TLX3‐driven T‐ALL
TAL1‐ and class II basic helix‐loop‐helix (bHLH) factor‐deregulated T‐ALL
Other subtypes of T‐ALL
Summary
Further reading

Chapter 6: Chronic myelogenous leukemia
Introduction
Epidemiology
Clinical presentation and natural history
Prognostic models
Molecular biology
Therapy
Allogeneic hematopoietic stem cell transplantation
Therapy of CML‐AP and CML‐BP
Philadelphia chromosome‐negative CML
Summary
Further reading

Chapter 7: Myeloproliferative neoplasms
Introduction
JAK–STAT pathways with a focus on JAK2
The JAK2 V617F mutation in Philadelphia‐negative MPNs
JAK2 V617F: One mutation yet multiple phenotypes
Other JAK2 mutations
MPL mutations in ET and MF
CALR mutations in ET and MF
Other somatic mutations in ET, MF, and PV
Chronic neutrophilic leukemia
Integration of molecular information into diagnostic algorithms and prognostication
Conclusions
Further reading

Chapter 8: Lymphoma genetics
Introduction
Techniques
Burkitt lymphoma
Diffuse large B‐cell lymphoma, not otherwise specified
Mantle cell lymphoma
Follicular lymphoma
Lymphoplasmacytic lymphoma
Marginal zone lymphoma
Chronic lymphocytic leukemia/small lymphocytic lymphoma
Anaplastic large cell lymphoma
Nodal T‐follicular helper (TFH) cell lymphoma
Peripheral T‐cell lymphoma, not otherwise specified
Conclusions
Further reading

Chapter 9: Molecular basis of chronic lymphocytic leukemia
Introduction and definition
Epidemiology
Genetic factors
Environmental factors
Molecular biology of CLL
B‐cell receptor signaling pathway
BCL2 family
CLL microenvironment
Impaired immunity in CLL
Richter transformation
Conclusion
Further reading

Chapter 10: The molecular biology of multiple myeloma
Introduction
Normal plasma cell development
Development of myeloma cell
Progression to multiple myeloma
Classification and risk stratification of myeloma
Conclusion
Further reading

Chapter 11: The molecular basis of bone marrow failure syndromes and red cell enzymopathies
Introduction
Conditions associated with bone marrow failure
Acquired bone marrow failure syndromes
Inherited GPI deficiency
Inherited bone marrow failure syndromes
Red cell enzyme deficiencies
Concluding remarks
Further reading

Chapter 12: Anemia of chronic disease
Introduction and definition
General principles
Diagnosis
Pathogenesis
Principles of treatment
Future treatments
Further reading

Chapter 13: Molecular basis of iron metabolism
Introduction
Mechanisms of iron transport
Sites of iron storage
Regulation of iron homeostasis
Iron disorders
Conclusions
Further reading

Chapter 14: Perspectives in genomics and sickle cell disease therapeutics
Introduction
Epidemiology of sickle cell disease
Pathophysiology
Mortality and life expectancy of SCD
Management of SCD
Exploring the missing heritability of fetal hemoglobin in Africa to uncover therapeutic targets
Investigating the prospect of RNA therapy for SCD
Developing genetic risk models for SCD complications
Conclusion and perspectives
Further reading

Chapter 15: Molecular coagulation and thrombophilia
Introduction
Blood coagulation
Regulation of blood coagulation
Molecular genetics of venous thromboembolism
Severe thrombophilia is a multigenic disease
Management of thrombophilia
Conclusions
Further reading

Chapter 16: The molecular basis of hemophilia
Introduction: clinical features of hemophilia
Inheritance of hemophilia
Molecular basis of hemophilia A
Molecular basis of hemophilia B
Inhibitor formation: etiology and clinical implications
Therapeutic applications of molecular biology to patient care
Conclusions
Further reading

Chapter 17: The molecular basis of von Willebrand disease
Introduction
Function of von Willebrand factor in primary hemostasis
Function of von Willebrand factor in intrinsic coagulation
Gene organization, synthesis, and multimeric structure of von Willebrand factor
von Willebrand disease and its classification
Genetic defects in von Willebrand disease
Treatment of von Willebrand disease
New therapies for von Willebrand disease
Further reading

Chapter 18: Platelet disorders
Normal platelet function
Diagnosis of platelet defects in bleeding disorders
Platelet adhesion disorders
Collagen receptor defects
Platelet aggregation defects
Agonist receptor defects
Defects in intracellular signaling pathways
Platelet secretion defects (storage pool disease)
Procoagulant regulation defects
Giant platelet syndromes and cytoskeletal defects
Transcription factor defects
Platelet protein polymorphisms and tendency to thrombosis
Further reading

Chapter 19: The molecular basis of blood cell alloantigens
Introduction
The major histocompatibility complex
Post‐transfusion purpura
Platelet refractoriness
Neonatal alloimmune thrombocytopenia
Neonatal alloimmune neutropenia
Transfusion‐related acute lung injury
Red blood cell antigens and molecular typing
Hemolytic disease of the fetus and newborn
Conclusions
Further reading
Chapter 20: Functions of blood group antigens
Introduction
Anion‐exchanger protein 1 (band 3 protein)
Rh proteins
Glycophorins C and D
Blood group antigen proteins that function as adhesion molecules
Blood group antigen proteins with other functions
Summary
Further reading
Chapter 21: Autoimmune hematological disorders
Introduction
The immune system
The spectrum of autoimmune diseases
Role of genetic factors
Mouse models of autoimmune disease
Human studies
Immune thrombocytopenia as a hematological model of autoimmune disease
Targeted versus untargeted therapies for autoimmune disease
Novel therapies for the treatment of ITP
Conclusions
Further reading
Chapter 22: Molecular therapeutics in hematology: gene therapy
Introduction
General comments on gene transfer/therapy
Viral vectors for gene transfer
Oncoretroviral gene transfer
Lentiviral gene transfer
Adenoviral gene transfer
Adeno‐associated virus gene transfer
Herpes simplex virus gene transfer
Genetic immunotherapy
Methods to improve gene therapy safety and suicide gene therapy
Conclusions
Further reading
Chapter 23: Pharmacogenomics
Introduction
Principles of pharmacogenomics
Pharmacogenomics to improve childhood ALL therapy
Pharmacogenomics to optimize oral antithrombotic therapy
Summary and challenges for the future
Further reading
Chapter 24: Cancer stem cells
The cancer stem cell concept
The cell of origin
Pre‐leukemic stem cells
CSC‐targeted therapies
Conclusion
Further reading
Chapter 25: CAR‐T cell therapy
History of CAR‐T cell therapy
CAR structure and function
CAR‐T cell manufacturing
CAR‐T disease‐specific clinical data
Sources of CAR‐T resistance
Toxicities of CAR‐T therapy
CAR‐T cells in the tumor microenvironment
References
Chapter 26: Molecular basis of transplantation
Introduction and definition
Principles and clinical indications of HCT
Exploiting HCT for resetting the immune system
Basic concepts in the immunology of allogeneic HCT
Graft‐versus‐host and graft‐versus‐leukemia
The pathogenesis of GvHD
Can GvHD and GvL be dissected?
New directions
Conclusions
Further readings

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