Review Articles
Vol. 12 No. 1 (2020): Mediterranean Journal of Hematology and Infectious Diseases, Volume 12, 2020
ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: August 10, 2020
Accepted: October 3, 2020
Accepted: October 3, 2020
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b-thalassemia is a hereditary disorder caused by defective production of b-globin chains of hemoglobin (Hb) that leads to an increased a/b globins ratio with subsequent free a-globins. Alpha globin excess causes oxidative stress, RBCs membrane damage, premature death of late-stage erythroid precursors, resulting in ineffective erythropoiesis.
The transforming growth factor b (TGF-b) superfamily signaling acts on biological processes, such as cell quiescence, apoptosis, proliferation, differentiation, and migration, and also plays an important role in the regulation of 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-b pathway by inhibiting the Smad2/3 cascade, thus alleviating anemia in patients with b-thalassemia and myelodysplastic syndromes.
In this review, we describe in extenso the TGF-b pathway, as well as the molecular and biological basis of activin receptors ligand traps, focusing on their role in various b-thalassemia experimental models. The most recent results from clinical trials on sotatercept and luspatercept will also be reviewed.
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How to Cite
“ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY” (2020) Mediterranean Journal of Hematology and Infectious Diseases, 12(1), p. e2020075. doi:10.4084/mjhid.2020.075.
Copyright (c) 2020 Irene Motta, Valentina Brancaleoni, Isabella Nava, Paola Delbini, Lorena Duca
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
