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The Molecular Basis of Blood Diseases, 3rd Edition

The Molecular Basis of Blood Diseases, 3rd Edition

This comprehensive text focuses on the pathophysiology of hematologic diseases. There is no field in which molecular techniques have been applied more fruitfully. Given the large amount of rapidly accumulating information in the field, this book fills a niche that will become increasingly important.

Each of the four editors is a distinguished investigator who has made important contributions to our understanding of blood disorders. Dr. George Stamatoyannopoulos is Professor of Medicine in the Division of Medical Genetics at the University of Washington School of Medicine in Seattle; Dr. Philip Majerus is Professor of Medicine and Biological Chemistry in the Division of Hematology/Oncology at the Washington School of Medicine in St. Louis; Dr. Roger Perlmutter is Executive Vice President of Basic Research at Merck Research Laboratories in Rahway, NJ; and Dr. Harold Varmus is President and Chief Executive Officer at Memorial Sloan-Kettering Cancer Center, and Professor of Cell Biology and Genetics at Cornell Medical School in New York. These giants in medicine, in turn, have assembled an outstanding group of contributors.

The book begins with a beautifully written chapter on stem cell biology that carefully describes the organization of hematopoiesis into stem cell compartments. An explanation of the general principles of hematopoietic stem cells, including their properties, identification, and purification, follows. The chapter concludes with a discussion of ex vivo expansion of hematopoietic stem cells, a potentially important strategy in stem cell transplantation.

In the second chapter, Dr. Ken Kaushansky, who has made numerous seminal observations regarding thrombopoiesis, describes hematopoietic growth factors and their receptors. The chapter also reviews the potential role of hematopoietic growth factors in the pathogenesis of various diseases, addressing, for example, the ability of erythropoietin to stimulate erythropoiesis and improve renal failure. The 5q- syndrome, a well-defined myelodysplastic syndrome, is described. Interestingly, the genes for many hematopoietic growth factors are located on the long-arm of chromosome 5. The role of excessive erythropoietin production in polycythemic states, of mutations in the thrombopoietin gene in patients with familial essential thrombocythemia, and of several cytokines including tumor necrosis factor in the pathogenesis of juvenile chronic myeloid leukemia are also addressed in this chapter.

The third chapter, by Dr. Stuart Orkin from Harvard Medical School, successfully presents the complicated subject of transcription factors so that it is understandable to the non-laboratory-based hematologist or oncologist. The chapter begins with a description of the transcription factors responsible for the development and maintenance of the early progenitors of the hematopoietic stem cell and then discusses the factors responsible for the commitment to myeloid and erythroid lineages. It concludes by addressing the factors responsible for the development of the lymphoid lineage.

As a natural progression, the following chapter by Dr. James Ihle discusses signal transduction as it pertains to hematopoiesis, concluding part I of the book. A large portion of the chapter is devoted to the activation of tyrosine kinase receptors and the consequences of phosphorylation of several substrates. This is particularly important as it provides a background for understanding the mechanism of action of the new bcr-abl tyrosine kinase receptor inhibitor imatinib mesylate (Gleevec) in patients with bcr-abl gene rearrangements, such as those with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia.

Part II focuses on red cells and comprises the next six chapters. Chapters 5 through 7 follow in logical sequence and are authored by four individuals (Drs. George Stamatoyannopoulos, Frank Grosveld, D. J. Weatherall, and H. Franklin Bunn) who have made important contributions to our understanding of hemoglobin production and regulation, the thalassemias and other hemoglobinopathies including sickle cell disease. Chapter 5, entitled "Hemoglobin Switching," also makes an otherwise complicated area quite understandable. The next two chapters focus on the erythrocyte, the structure of its membrane, disorders of red cell cytoskeletal proteins, and red cell membrane antigens.

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