ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY
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 precurso...
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| Format: | Article |
| Language: | English |
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PAGEPress Publications
2020-10-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
| Online Access: | http://www.mjhid.org/index.php/mjhid/article/view/4358 |
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| author | Irene Motta Valentina Brancaleoni Isabella Nava Paola Delbini Lorena Duca |
| author_facet | Irene Motta Valentina Brancaleoni Isabella Nava Paola Delbini Lorena Duca |
| author_sort | Irene Motta |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1ee4fa2a1f674da287972c0ce14444ab |
| institution | DOAJ |
| issn | 2035-3006 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj-art-1ee4fa2a1f674da287972c0ce14444ab2025-08-20T02:50:42ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062020-10-0112110.4084/mjhid.2020.075ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERYIrene MottaValentina BrancaleoniIsabella NavaPaola DelbiniLorena Ducab-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.http://www.mjhid.org/index.php/mjhid/article/view/4358 |
| spellingShingle | Irene Motta Valentina Brancaleoni Isabella Nava Paola Delbini Lorena Duca ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY Mediterranean Journal of Hematology and Infectious Diseases |
| title | ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY |
| title_full | ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY |
| title_fullStr | ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY |
| title_full_unstemmed | ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY |
| title_short | ACTIVIN RECEPTOR LIGAND FOR THR TREATMENT OF BETA-THALASSEMIA: a SERENDIPITOUS DISCOVERY |
| title_sort | activin receptor ligand for thr treatment of beta thalassemia a serendipitous discovery |
| url | http://www.mjhid.org/index.php/mjhid/article/view/4358 |
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