β-thalassemia is a hereditary disorder caused by defective production of β-globin chains of hemoglobin (Hb) that leads to an increased α/β globins ratio with subsequent free α-globins. Alpha globin excess causes oxidative stress, red blood cells membrane damage, premature death of late-stage erythroid precursors, resulting in ineffective erythropoiesis. The transforming growth factor β (TGF-β) superfamily signaling acts on biological processes, such as cell quiescence, apoptosis, proliferation, differentiation, and migration, and plays an essential role in regulating the hematopoiesis. This pathway can lose its physiologic regulation in pathologic conditions, leading to anemia and ineffective erythropoiesis. Activin receptor-ligand trap molecules such as Sotatercept and Luspatercept downregulate the TGF-β pathway, thus inhibiting the Smad2/3 cascade and alleviating anemia in patients with β-thalassemia and myelodysplastic syndromes. In this review, we describe in extenso the TGF-β pathway, as well as the molecular and biological basis of activin receptors ligand traps, focusing on their role in various β-thalassemia experimental models. The most recent results from clinical trials on sotatercept and luspatercept will also be reviewed.

Activin receptor-ligand trap for the treatment of β-thalassemia : a serendipitous discovery / V. Brancaleoni, I. Nava, P. Delbini, L. Duca, I. Motta. - In: MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES. - ISSN 2035-3006. - 12:1(2020 Nov), pp. e2020075.1-e2020075.10. [10.4084/MJHID.2020.075]

Activin receptor-ligand trap for the treatment of β-thalassemia : a serendipitous discovery

V. Brancaleoni;I. Nava;P. Delbini;L. Duca;I. Motta
2020-11

Abstract

β-thalassemia is a hereditary disorder caused by defective production of β-globin chains of hemoglobin (Hb) that leads to an increased α/β globins ratio with subsequent free α-globins. Alpha globin excess causes oxidative stress, red blood cells membrane damage, premature death of late-stage erythroid precursors, resulting in ineffective erythropoiesis. The transforming growth factor β (TGF-β) superfamily signaling acts on biological processes, such as cell quiescence, apoptosis, proliferation, differentiation, and migration, and plays an essential role in regulating the hematopoiesis. This pathway can lose its physiologic regulation in pathologic conditions, leading to anemia and ineffective erythropoiesis. Activin receptor-ligand trap molecules such as Sotatercept and Luspatercept downregulate the TGF-β pathway, thus inhibiting the Smad2/3 cascade and alleviating anemia in patients with β-thalassemia and myelodysplastic syndromes. In this review, we describe in extenso the TGF-β pathway, as well as the molecular and biological basis of activin receptors ligand traps, focusing on their role in various β-thalassemia experimental models. The most recent results from clinical trials on sotatercept and luspatercept will also be reviewed.
TGF-β; β-thalassemia
Settore MED/09 - Medicina Interna
Settore MED/15 - Malattie del Sangue
Article (author)
File in questo prodotto:
File Dimensione Formato  
4358-Article Text-29246-1-10-20201023.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 998.44 kB
Formato Adobe PDF
998.44 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/794809
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 5
social impact