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

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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