Abstract:
The thalassemias together with sickle cell anemia and its variants are the world's most common form of inherited anemia and in economically undeveloped countries still account for tens of thousands of premature deaths every year. In developed countries, treatment of thalassemia is still far from ideal, requiring lifelong transfusion or allogeneic bone marrow transplantation. Clinical and molecular genetic studies over the past 50 years have demonstrated how co-inheritance of modifier genes, which alter the balance of α-like and β-like globin gene expression, may transform severe, transfusion dependent thalassemia into mild forms of anemia. Most attention has been paid to pathways that increase γ-globin expression and hence the production of fetal hemoglobin. Here we review the evidence that reduction of α-globin expression may provide an equally plausible approach to ameliorate clinically severe forms of β-thalassemia, in particular, the very common subgroup of patients with HbE β-thalassemia which make up approximately half of all patients born each year with severe β-thalassemia.
