Hematology 2005
© 2005 The American Society of Hematology
Pathophysiology of ß Thalassemia—A Guide to Molecular Therapies
Swee Lay Thein
Correspondence: Swee Lay Thein, MD, Professor of Molecular Haematology, King’s College Hospital, Guy’s King’s & St Thomas’ School of Medicine, Kings College London, Denmark Hill, London SE5 9PJ, UK; Phone +44 (0)20 7346 1682/1689; Fax +44 (0)20 7346 5178, sl.thein{at}kcl.ac.uk
Abstract
The central mechanism underlying the pathophysiology of the ß thalassemias can be related to the deleterious effects of imbalanced globin chain synthesis on erythroid maturation and survival. An imbalance of the 
/non- globin chains leads to an excess of unmatched globin which precipitates out, damaging membrane structures leading to accelerated apoptosis and premature destruction of the erythroid precursors in the bone marrow (ineffective erythropoiesis). Close observation of the genotype/phenotype relationships confirms the pathophysiological mechanism and provides clues to molecular therapies, all of which aim to reduce the /non- chain imbalance. They include inheritance of the milder forms of ß thalassemia, co-inheritance of thalassemia, or genetic factors (quantitative trait loci, QTLs) for increasing 
globin expression. Currently, the most promising molecular therapeutic approaches include increasing ß globin gene expression by stem cell gene therapy and increasing globin expression using pharmacological agents or by transduction of the globin genes.
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Copyright © 2005 by the American Society of Hematology.
