Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management

In this short review, we presented and discussed studies on the expression of globin genes in beta-thalassemia, focusing on the impact of alpha-globin gene expression and alpha-globin modifiers on the phenotype and clinical severity of beta-thalassemia. We first discussed the impact of the excess of free alpha-globin on the phenotype of beta-thalassemia. We then reviewed studies focusing on the expression of alpha-globin-stabilizing protein (AHSP), as a potential strategy of counteracting the effects of the excess of free alpha-globin on erythroid cells. Alternative processes controlling alpha-globin excess were also considered, including the activation of autophagy by beta-thalassemia erythroid cells. Altogether, the studies reviewed herein are expected to have a potential impact on the management of patients with beta-thalassemia and other hemoglobinopathies for which reduction in alpha-globin excess is clinically beneficial.