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The many different kinds of blood cells found in the human body are derived from multi-potential stem cells, which are induced to differentiate into one or another cell type by the action of regulatory proteins or growth factors. This volume looks at the way that binding of these proteins to specific receptors causes changes in gene expression in the nucleus and the activity of certain enzymes in the cytoplasm, committing the cell to a particular developmental pathway. Also discussed are recently established clinical applications and clinical trials of new techniques.
This book presents a masterful overview of the mechanics of blood cell formation and the factors that control blood cell growth. Cells circulating in the blood perform functions essential for the survival of organisms, yet blood cells and associated blood-cell-forming (hemopoietic) tissues have certain features that make them quite different from other vital organs in the body. These features include the short life span of mature blood cells, the multiplicity of blood cell types, and the wide dispersion of hemopoietic tissue in the body. The regulation of hemopoiesis in response to emergencies such as blood loss or infections is an exceedingly complex process. However, our knowledge of hemopoietic growth factors, known generally as colony-stimulating factors or CSFs, has made exciting advances in recent years. This book provides a leading authority's review of the purification and cloning of CSFs and their actions in regulating white blood cell production in the body. Donald Metcalf also examines the role of CSFs in controlling resistance to infections and in the initiation and suppression of myeloid leukemia. Metcalf's involvement at the center of this research from its inception to the present day enables him to give a historical view as well as a lucid summary of recent research. In addition, he addresses the broader question of the relation between growth control and cancer development. This excellent synopsis should be of particular interest to hematologists, virologists, general clinicians, and medical students.
Although much is known with respect to blood cell formation and function, many new concepts in the areas of the regulation of hematopoietic stem cell commitment and the subsequent survival, proliferation, and differentiation of progenitors have been elucidated in the last five years. Our understanding of the microenvironment where stem cells reside and commit to distinct blood types (the niche) has grown significantly in recent years. Furthermore, blood cells have been used as the key model system to study microRNA function and the role of microRNAs in the transformation of normal cells into cancer cells. The current volume Molecular Basis of Hematopoiesis, edited by Amittha Wickrema & Barbara Kee, provides the most recent developments in the area in addition to a chapter on the utilization of basic science knowledge for the treatment of blood diseases. Each chapter in this book has been written and edited by faculty in major academic and research institutions around the world, who are pushing the frontiers of research in this important area.
This volume of Molecular Biology of Hematopoiesis is dedicated to John W. Adam son, M. D. , Tadamitsu Kishimoto, M. D. , Robert C. Gallo, M. D. , Arthur W. Nienhuis, M. D. , and Franco Mandelli, M. D. , for their contributions in developing an overall view of the state-of-the-art knowledge in the field of hematopoiesis. Richard Champlin, among other renowned clinicians, presented updated information on stem cells and T-cell depletion for bone marrow transplant. A clinical update on thrombopoietin was presented by Pamela Hunt of Amgen and by Kenneth Kaushansky. Arthur Nienhuis' and Katherine Turner's contribu tions to our current knowledge and advances in the fields of growth factors and gene transfer were also recognized during the 9th Symposium on Molecular Biology of Hematopoiesis in Genoa. The chapters cover such diverse areas as preclinical and clinical updates on growth factors and positive and negative regulatory molecules. "Advances in Leukemia: Mechanism and Treatment by Interferon" was presented by Professor Sante Tura. Readers will find presentation of exciting advances that have occurred in the area of hematopoiesis. The elucidation of gene structures of key growth factor proteins such as IL-12 and IL-II will lead to new insights and new approaches in understanding the regulation of hematopoiesis, as well as application of new growth factors.
This book gives an update on the inhibitory mechanisms involved in the various steps of hematopoietic stem cell proliferation and differentiation. The authors report the latest research advances, factors that control the cell cycle, receptors function, molecular approaches, the in vivo and in vitro effects of several inhibitors, the inhibition of hematopoiesis by viruses, protecting the bone marrow. The book contains the latest results published by the best international specialists and will be fascinating reading for all those interested in this subject.
Hematopoiesis, or the process of blood formation, has been extensively studied at both basic and clinical levels. Human diseases such as thalassemia, immunodeficiency, and leukemia represent defects in this process. Approaches to treat these disorders have required a basic understanding of the biology of blood cells. For instance, hemapoietic stem cell replacement or bone marrow transplantation has been used to ameliorate disease. This volume focuses on hematopoiesis at a cellular and molecular level, and establishes the basis for clinical manipulation of hematopoietic cells for therapeutic benefit. In Part I, the cellular characteristics of progenitors and stem cells are explored. Emphasis is placed on purification of stem cells and both in vitro and in vivo assays. The regulation of normal and leukemis stem cells is illustrated. An excellent discussion of potential use of these cells for gene therapy concludes this section. Hemapoiesis is easily studied during embryogenesis. Part II develops the concept of the waves of hemapoiesis during development. Comparative hematology is making a major comeback as a field in the 1990's. One hope is that general principles of hematopoiesis will be established by studying many models and systems. Part III delves into critical factors that regulate hematopoiesis, including both intracellular and extracellular signals. Part IV and V describe lineage programs for myeloid and lymphoid lineages. These chapters are meant to be illustrative of the different cell fates, but are not exhaustive. Part VI examines the genetics of hematopoisis, particularly in animal models. The hematopoietic system is in constant contact with stromal cells and endothelial cells during development and in the adult. Evidence suggests that endothelial cells and blood cells may arise from a common progenitor, the hemangioblast. Part VII and VIII discuss the stromal and endothelial cells with the emphasis on their interaction with hematopoietic cells.
This volume of Molecular Biology of Hematopoiesis is dedicated to many inter national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. The continuous support of the Presidents of the meeting, Professor F. Takaku, President of Jichi University, and E. D. Thomas, Nobel Laureate, was greatly acknowledged, especially Professor Takaku, for his vision and support for development of gene therapy in Japan. New information on BMT for autoimmune disease and organ transplantation was presented at the symposium and is published in this volume. Several new findings on gene therapy/transfer into HSC were presented by E. F. Vanin and A. Nienhuis, K. Humphries, 1. A. Nolta, H. E. Heslop, and M. K. Brenner. Professors S. Asano and K. Tani presented new studies on gene transfer into primates. Among the highlights were the new papers on gene transfer presented by G. Wage maker, N. G. Abraham, and M. Onoderea from R. M. BJaese's group. The use of BMT for organ transplant and autoim mune disease was updated and a representative paper is presented in this volume.