A particular type of anemia in humans, called β-thalassemia, results from a severe reduction or absence of the normal β-globin chain of hemoglobin. However, the γ-globin chain, normally only expressed during fetal development, can functionally substitute for β-globin. A variety of studies have explored the use of the nucleoside 5-azacytidine for the expression of γ-globin in adult patients with β-thalassemia.

How might 5-azacytidine lead to expression of γ-globin in adult patients?

Key Concepts

β-thalassemia

β-thalassemia is a genetic blood disorder characterized by reduced or absent production of the β-globin chain of hemoglobin, leading to anemia. This condition is caused by mutations in the HBB gene, which encodes the β-globin subunit. The severity of the disease can vary, with some individuals experiencing mild symptoms while others may require regular blood transfusions.

γ-globin chain

The γ-globin chain is a component of fetal hemoglobin (HbF), which is produced during fetal development and has a higher affinity for oxygen than adult hemoglobin. In normal circumstances, γ-globin expression decreases after birth, and β-globin takes over. However, in patients with β-thalassemia, reactivating γ-globin expression can help compensate for the lack of β-globin, improving oxygen transport in the blood.

5-azacytidine

5-azacytidine is a nucleoside analog that functions as a DNA methyltransferase inhibitor, leading to the demethylation of DNA. This process can reactivate silenced genes, including those responsible for γ-globin production. In the context of β-thalassemia, 5-azacytidine has been studied for its potential to induce the expression of γ-globin in adult patients, thereby alleviating some symptoms of the disease.