Ineffective Erythropoiesis: Associated Factors and Their Potential as Therapeutic Targets in Beta-Thalassaemia Major

Abstract

Beta-thalassaemia ( b -thal.) is single-gene disorder that exhibits much clinical variability. b -thal. major is a major health problem, and the only method of curing is allogenic bone-marrow transplantation, which is not available to everyone and not without risk. The underlying pathogenesis of b -thal. major is due to ineffective erythropoiesis (IE), which is characterized by increased proliferative activity that fails to produce sufficient functional red blood cells. In b -thal. patients, the severity of the IE is mainly responsible for the hallmarks of the disease’s presentation, sequalae and complications. This review discusses the mechanisms of IE, the factors that contribute to it and the potential therapies for targeting these factors to improve patients’ clinical phenotypes.