Pathophysiology of β Thalassemia—A Guide to Molecular Therapies
Open Access
- 1 January 2005
- journal article
- Published by American Society of Hematology in Hematology-American Society Hematology Education Program
- Vol. 2005 (1), 31-37
- https://doi.org/10.1182/asheducation-2005.1.31
Abstract
The central mechanism underlying the pathophysiology of the β thalassemias can be related to the deleterious effects of imbalanced globin chain synthesis on erythroid maturation and survival. An imbalance of the α/non-α globin chains leads to an excess of unmatched α 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 α/non-α chain imbalance. They include inheritance of the milder forms of β thalassemia, co-inheritance of α thalassemia, or genetic factors (quantitative trait loci, QTLs) for increasing γ globin expression. Currently, the most promising molecular therapeutic approaches include increasing β globin gene expression by stem cell gene therapy and increasing γ globin expression using pharmacological agents or by transduction of the γ globin genes.Keywords
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