Ineffective Erythropoiesis: Associated Factors and Their Potential as Therapeutic Targets in Beta-Thalassaemia Major
Heba Alsaleh
Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia.
Sarina Sulong
Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia.
Bin Alwi Zilfalil
Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
Rosline Hassan *
Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia.
*Author to whom correspondence should be addressed.
Abstract
Beta-thalassaemia (β-thal.) is single-gene disorder that exhibits much clinical variability. β-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 β-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 β-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.
Keywords: Thalassaemia, ineffective erythropoiesis, gene therapy, apoptosis