Book Review

Molecular Haematology

N Engl J Med 2000; 343:371August 3, 2000

Article

Molecular Haematology
Edited by Drew Provan and John Gribben. 240 pp., illustrated. Malden, Mass., Blackwell Science, 2000. $190. ISBN: 0-632-05037-3

The highly specialized functions of blood cells and their ready accessibility account in large part for the rapidly expanding knowledge of the molecular basis of hematologic diseases. In his foreword to this book, Max Perutz states that the day he spent trying to correlate amino acid substitutions in the globin molecule with the symptoms they may cause was “one of the most exciting days” in his scientific life. In Molecular Haematology, Provan and Gribben aim to show the ways in which molecular biology has profoundly influenced our understanding of blood diseases and the ways in which molecular techniques can be used in the diagnosis and treatment of these disorders.

The contributions cover the main fields of hematology, from inherited diseases to neoplasia. Several chapters deal with diagnostic techniques (molecular cytogenetics and the detection of minimal residual disease) and treatment (hematopoietic growth factors and gene therapy). Readers without a strong background in molecular biology will find detailed explanations, numerous diagrams, and an overview of recent advances in cancer-cell biology, with particular emphasis on leukemia and lymphoma.

Several cancers are covered in separate chapters. Chronic myeloid leukemia is the best example of a neoplastic disease with a distinctive gene rearrangement (the BCR-ABL fusion gene), and one in which cytogenetic and molecular studies are routinely performed to monitor the efficacy of treatment. The development of specific tyrosine kinase inhibitors of the BCR-ABL gene product, one of which is already being evaluated in a clinical trial, is one of the most exciting accomplishments of molecular medicine. In other diseases, such as the myelodysplastic syndromes and myeloproliferative disorders, the molecular defects are less well characterized, but this textbook will help readers learn the current understanding of these disorders. The heterogeneity of non-Hodgkin's lymphomas has recently been clarified with the help of molecular cytogenetic techniques, and the major pathologic entities and their corresponding molecular abnormalities have now been characterized, as discussed in this book.

More details on normal lymphoid differentiation would help readers understand lymphoid neoplasms better. For example, recent data suggest that the mutation status of immunoglobulin genes may be important with respect to the biologic and clinical features of chronic lymphoid leukemia. Similarly, several studies have now demonstrated that most cases of Hodgkin's disease arise from cells committed to the B-cell lineage. Additional molecular abnormalities, such as overexpression of Bcl-2 or p53 gene mutations that influence the outcome in lymphoma, might have been emphasized, since these findings are likely to influence treatment choices in the future.

The molecular pathology of hemoglobin is detailed in two chapters dealing with defects in the synthesis of globin chains in thalassemia and mutant hemoglobin molecules, such as hemoglobin S. Recent developments in the understanding of hemophilia and thrombophilia are considered, with practical recommendations regarding screening tests for genetic susceptibility to thrombosis. The molecular basis of anemia is reviewed, although this chapter focuses on rare inherited or acquired anemias. The apparent omission of anemias with common causes, such as iron-deficiency anemia and acquired hemolytic anemia, is easily explained by their diverse origins, which are usually unrelated to the biology of the hematopoietic system and do not fall within the scope of this book. For the same reason, diseases such as immune thrombocytopenia are not discussed in this work.

The main feature of Molecular Haematology is its emphasis on the practical impact of major developments in molecular biology. The style is very readable for those unfamiliar with molecular biology or specialized aspects of hematology. There is a good balance between descriptions of basic mechanisms and discussions of their implications for clinical practice. The authors' opinions of innovative strategies enrich the work without compromising its length. This book therefore constitutes a valuable manual, rather than an extended textbook. Editorial choices, such as restricting bibliographic references to the essential and the extensive use of didactic figures, result in a book that is easy and appealing to consult.

Molecular medicine is rapidly evolving, and innovative diagnostic and therapeutic strategies, as outlined in this book, will continue to develop. In their preface, the editors suggest that future editions are planned; with further enrichments, this book may constitute an excellent reference and provide an example for works on other medical specialties to follow.

Gilles Salles, M.D., Ph.D.
Hospices Civils de Lyon, Pierre-Bénite CEDEX 69495, France