Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs
β-thalassaemia is a rare genetic condition caused by mutations in the β-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of ineffective erythropoiesis (IE). The role of multiple mechanisms involved in the pathophysiology of the disease has been recently unrav...
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doaj-9aae6efd9a1e43b59730648b5a28d8bb2021-07-15T15:38:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-01227229722910.3390/ijms22137229Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by DrugsFilomena Longo0Andrea Piolatto1Giovanni Battista Ferrero2Antonio Piga3Department of Clinical and Biological Sciences, University of Torino, 10043 Torino, ItalyDepartment of Clinical and Biological Sciences, University of Torino, 10043 Torino, ItalyDepartment of Clinical and Biological Sciences, University of Torino, 10043 Torino, ItalyDepartment of Clinical and Biological Sciences, University of Torino, 10043 Torino, Italyβ-thalassaemia is a rare genetic condition caused by mutations in the β-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of ineffective erythropoiesis (IE). The role of multiple mechanisms involved in the pathophysiology of the disease has been recently unravelled. The unbalanced production of α-globin is a major source of oxidative stress and membrane damage in red blood cells (RBC). In addition, IE is tightly linked to iron metabolism dysregulation, and the relevance of new players of this pathway, i.e., hepcidin, erythroferrone, matriptase-2, among others, has emerged. Advances have been made in understanding the balance between proliferation and maturation of erythroid precursors and the role of specific factors in this process, such as members of the TGF-β superfamily, and their downstream effectors, or the transcription factor GATA1. The increasing understanding of IE allowed for the development of a broad set of potential therapeutic options beyond the current standard of care. Many candidates of disease-modifying drugs are currently under clinical investigation, targeting the regulation of iron metabolism, the production of foetal haemoglobin, the maturation process, or the energetic balance and membrane stability of RBC. Overall, they provide tools and evidence for multiple and synergistic approaches that are effectively moving clinical research in β-thalassaemia from bench to bedside.https://www.mdpi.com/1422-0067/22/13/7229thalassaemiaineffective erythropoiesiserythroid precursorsiron dysregulationfoetal haemoglobinnew treatments |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Filomena Longo Andrea Piolatto Giovanni Battista Ferrero Antonio Piga |
spellingShingle |
Filomena Longo Andrea Piolatto Giovanni Battista Ferrero Antonio Piga Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs International Journal of Molecular Sciences thalassaemia ineffective erythropoiesis erythroid precursors iron dysregulation foetal haemoglobin new treatments |
author_facet |
Filomena Longo Andrea Piolatto Giovanni Battista Ferrero Antonio Piga |
author_sort |
Filomena Longo |
title |
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs |
title_short |
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs |
title_full |
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs |
title_fullStr |
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs |
title_full_unstemmed |
Ineffective Erythropoiesis in β-Thalassaemia: Key Steps and Therapeutic Options by Drugs |
title_sort |
ineffective erythropoiesis in β-thalassaemia: key steps and therapeutic options by drugs |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-07-01 |
description |
β-thalassaemia is a rare genetic condition caused by mutations in the β-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of ineffective erythropoiesis (IE). The role of multiple mechanisms involved in the pathophysiology of the disease has been recently unravelled. The unbalanced production of α-globin is a major source of oxidative stress and membrane damage in red blood cells (RBC). In addition, IE is tightly linked to iron metabolism dysregulation, and the relevance of new players of this pathway, i.e., hepcidin, erythroferrone, matriptase-2, among others, has emerged. Advances have been made in understanding the balance between proliferation and maturation of erythroid precursors and the role of specific factors in this process, such as members of the TGF-β superfamily, and their downstream effectors, or the transcription factor GATA1. The increasing understanding of IE allowed for the development of a broad set of potential therapeutic options beyond the current standard of care. Many candidates of disease-modifying drugs are currently under clinical investigation, targeting the regulation of iron metabolism, the production of foetal haemoglobin, the maturation process, or the energetic balance and membrane stability of RBC. Overall, they provide tools and evidence for multiple and synergistic approaches that are effectively moving clinical research in β-thalassaemia from bench to bedside. |
topic |
thalassaemia ineffective erythropoiesis erythroid precursors iron dysregulation foetal haemoglobin new treatments |
url |
https://www.mdpi.com/1422-0067/22/13/7229 |
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