Understanding globin regulation in β-thalassemia: it’s as simple as α, β, γ, δ
Arthur Bank
Arthur Bank
View: Text | PDF
Commentary

Understanding globin regulation in β-thalassemia: it’s as simple as α, β, γ, δ

Abstract

A vast excess of α-globin production and inadequate γ-globin compensation lead to the development of severe anemia in human β-thalassemia. Newly identified modifiers of α- and γ-globin synthesis and insights into the mechanisms of globin regulation provide the tools for potential new approaches to treating this and other red blood cell disorders. In the study by Han and colleagues in this issue of the JCI, the activity of a heme-regulated protein, HRI, is shown to modulate the accumulation of excess α-globin chains in murine β-thalassemia and to decrease the severity of the disease.

Authors

Arthur Bank

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
The human globin loci and their role in β-thalassemia. (A) The β-LCR and...
The human globin loci and their role in β-thalassemia. (A) The β-LCR and structural genes (ε, Gγ, Aγ, δ, and β) within the β-globin locus on chromosome 11 are shown. The Corfu deletion, which includes part of the structural δ-globin gene and γ_δ intergenic sequences, is also shown. (B) The α-globin locus is shown with the ζ- and 2 α-globin genes on chromosome 16. (C) In early fetal life, the α- and γ-globin chains combine to form HbF (α2γ2), the main β-globin_like globin during the remainder of fetal life and early postnatal life. In late postnatal and adult life, normal hemoglobin (HbA, α2β2) predominates. In homozygous β-thalassemia, decreased or absent β-globin production leads to decreased or absent HbA levels, respectively. The synthesis of γ-globin does not increase enough to compensate for the reduced or absent β-globin level. As a result, excess α-globin accumulates and precipitates in erythroid cells and causes damage due to the action of ROS and apoptosis of the damaged cells. Severe anemia results.