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Hematopoietic Stem Cell Biology

Hematopoietic stem cells (HSCs) are characterized by their unique ability to self-renew and give rise to the entirety of the blood and immune system throughout the lifetime of an individual. HSCs are very rare cells, representing approximately one in 100,000 bone marrow (BM) cells in the adult. The concept of the existence of an HSC that is capable of reconstituting hematopoiesis in vivo was first introduced…

Pharmacogenomics and Hematologic Diseases

It is widely recognized that heritable genetic variation (i.e., genotypes or haplotypes) can translate into inherited phenotypes, some of which predispose to or cause diseases and others alter response to treatment. One aim of medical genetics and pharmacogenomics (PGx) is to understand the myriad associations between inherited genotypes and specific phenotypes of disease or drug response, with the ultimate goal of better defining the risk for,…

Protein Architecture: Relationship of Form and Function

Previous chapters outline the central dogma of mlecular biology: the storage of genetic information in DNA and its regulated transcription into messenger RNA and eventual translation into proteins. In this chapter, we briefly outline the chemical structure of proteins and their posttranslational modifications (PTMs). We explain how the properties of the 20 amino acids of which proteins are composed allow these polymers to fold into compact,…

Signaling Transduction and Metabolomics

Hematopoiesis is a cellular process in which self-renewing stem progenitor cells differentiate into mature blood cells, which carry out specific biologic functions. These functions include oxygen delivery, clot formation, and immune responses, including defense of the host from infection and inflammation. Homeostasis of the whole hematopoietic system in vivo requires a tight control of systems and networks governing proliferation, cell fate, cell death, differentiation, cell–cell interaction,…

Genome Editing

Genome editing is a rapidly developing field in which the genome of cells is modified with single nucleotide precision. This degree of precision is not achievable by other forms of genetic engineering, including contemporary lentiviral vectors, recombinases, or transposases. Not only is genome editing precise in the location of the changes made, but it is highly flexible and robust in the types of changes that can…

Regulation of Gene Expression in Hematology

Introduction The function of a cell is not only determined by the sum of the specific RNAs and proteins expressed but also by their metabolism, modification, and localization. To understand how a cell behaves, one must understand how the expression of genes, translation of transcripts, and processing of proteins are regulated. Through concerted regulation of these processes, hematopoietic stem cells (HSCs) maintain a balance between quiescence…

Genomic Approaches to Hematology

Introduction The publication of the sequence of the human genome in 2001 heralded a new era in biomedical research and delivered a novel perspective on the biologic basis of the leukemias and lymphomas. A major tenet of these new approaches was their emphasis on the generation of large unbiased datasets as a means of discovery. The rapid application of this methodology combined with ready access to…

Epigenomics in Hematology

Epigenetics can be defined as inheritance of variation, above and beyond changes in the DNA sequence. In other words, epigenetics comprises the study of how cells sharing the same exhaustive DNA blueprint can appear and function so distinctly as white blood cells, hepatocytes, neurons, etc. Whereas the genome contains all of the vital information to direct the development of an organism, the epigenome dynamically filters and…

Anatomy and Physiology of the Gene

Normal blood cells have limited life spans; they must be replenished in precise numbers by a continuously renewing population of progenitor cells. Homeostasis of the blood requires that proliferation of these cells be efficient yet strictly constrained. Many distinctive types of mature blood cells must arise from these progenitors by a controlled process of commitment to, and execution of, complex programs of differentiation. Thus developing red…

Appendix

Chapter Outline Preparation of commonly used reagents 561 Water 561 Anticoagulants and preservative solutions 561 Buffers 562 Preparation of glassware 564 Cleaning slides 564 Cleaning glassware 564 Sizes of tubes 565 Speed of centrifugation 565 Statistical procedures 565 Calculations 566 Analysis of differences by t -test 566 Analysis of variation by F -ratio 566 Automated (mechanical) pipettes 567 Autodiluters 567 Preparation of commonly used reagents Water…

Haematology in Under-Resourced Laboratories

Introduction: types of laboratories In most countries, there are likely to be some laboratories with limited resources, but in under-resourced countries, the majority of laboratories face chronic shortages of trained staff, low morale, inadequate and poorly maintained equipment and erratic supplies of reagents and essential supplies. These factors have a major impact on the range and quality of services offered. Many laboratories lack the highly sophisticated…

Quality Assurance

Quality assurance (QA) in the haematology laboratory is intended to ensure reliable diagnostic test results with the necessary degree of accuracy and precision. There are some key definitions in QA that are fundamental to an understanding of its practice ( Table 25-1 ). Table 25-1 Some key definitions used in quality assurance Specificity Measures only the analyte of interest Accuracy The closeness of agreement between the…

Laboratory Organisation, Management and Safety

Acknowledgement The authors wish to acknowledge the major contribution of Dr Mitchell Lewis, the author or co-author of this chapter in previous editions. The services provided by laboratories are an essential and fundamental component of health systems across the globe. The essential functions of a haematology laboratory are (1) to provide clinicians with timely, unambiguous and meaningful information to assist in the clinical diagnosis of disease…

Approach to the Diagnosis and Classification of Blood Cell Disorders

Common presentations of haematological diseases An abnormal blood count or blood cell morphology does not necessarily indicate a primary haematological problem because it may reflect an underlying nonhaematological condition or may be the result of therapeutic interventions. Anaemia occurs in many conditions, but a primary blood disease should be considered when a patient has splenomegaly, lymphadenopathy, a bleeding tendency or thrombosis and/or nonspecific symptoms characteristic of…

Laboratory Aspects of Blood Transfusion

Safe and effective blood transfusion requires the combined efforts of blood transfusion services, biomedical scientists and clinicians to ensure the highest standards are applied to all the systems in a complex process from ‘vein to vein’. This chapter provides a description of the laboratory framework required to provide the right blood components to the right patients at the right time. The increased awareness of what can…

Blood Cell Antigens and Antibodies: Erythrocytes, Platelets and Neutrophils

Erythrocytes Red cell antigens Since Landsteiner’s discovery in 1901, that human blood groups existed, a vast body of serological, genetic and biochemical data on red cell (blood group) antigens has been accumulated. More recently, the biological functions of some of these antigens have been appreciated. A total of 30 blood group systems have been described ( Table 21-1 ). Each system is a series of red…

Laboratory Control of Anticoagulant, Thrombolytic and Antiplatelet Therapy

Anticoagulant and antithrombotic therapy is given to prevent formation or propagation of thrombi. Anticoagulant drugs, unlike fibrinolytic agents, have little if any effect on an already-formed thrombus. There are five main classes of drugs that require consideration: 1. Coumarins and indanediones, which are orally active and act by interfering with the γ-carboxylation step in the synthesis of the vitamin K-dependent factors (see p. 371). 2. Heparin, heparinoids…

Investigation of a Thrombotic Tendency

Introduction to thrombophilia Investigations to identify an acquired or inherited thrombotic tendency are most frequently carried out in patients who develop venous or arterial thrombosis at a young age, in those who have a strong family history of such events or have thrombosis at an unusual site and in individuals of all ages with recurrent episodes of thromboembolism. In recent years the utility of these tests,…

Investigation of Haemostasis

Components of normal haemostasis The haemostatic mechanisms have several important functions: (1) to maintain blood in a fluid state while it remains circulating within the vascular system; (2) to arrest bleeding at the site of injury or blood loss by formation of a haemostatic plug; (3) to limit this process to the vicinity of the damage and (4) to ensure the eventual removal of the plug…

Diagnostic Radioisotopes in Haematology

Radioactive isotopes must be distinguished from nonradioactive isotopes of the same element. The radioactive forms are usually referred to as radionuclides or radioisotopes. These terms are interchangeable and in this chapter, the latter term is used. Methods using radioisotopes have an important place in haematological diagnosis. Tests that may be undertaken in haematology departments include total blood volume (TBV), red cell survival studies and, occasionally, ferrokinetic…