AUTHOR=Sanchez-Villalobos Maria , Blanquer Miguel , Moraleda Jose M. , Salido Eduardo J. , Perez-Oliva Ana B. 

TITLE=New Insights Into Pathophysiology of β-Thalassemia

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.880752

DOI=10.3389/fmed.2022.880752

ISSN=2296-858X

ABSTRACT=β-thalassemia is a disease caused by genetic mutations as a result of single nucleotide substitution, small deletions or insertions within the β-globin gene, or in rare cases, gross deletions into the β-globin gene. These mutations affect globin-chain subunits within the hemoglobin tetramer that leads to an imbalance in the α/β-globin chain ratio, with an excess of free α-globin chains that triggers the most important pathogenic events of the disease: ineffective erythropoiesis, chronic anemia/chronic hypoxia, compensatory hemopoietic expansion and iron overload.  
Based on advances in our knowledge of the pathophysiology of β-thalassemia, in recent years, emerging therapies and clinical trials are being conducted and can be classified into three major categories based on the different approach features of the underlying pathophysiology: correction of the globin chain imbalance; reverse ineffective erythropoiesis; and improving iron overload. However, pathways such as the dysregulation of transcriptional factors, activation of the inflammasome, or approach to mechanisms of bone mineral loss, remain unexplored for future therapeutic targets. 	
In this review, we update the main pathophysiological pathways involved in β-thalassemia, focusing on the development of new therapies directed at new therapeutic targets.