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Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia

Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and β-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or β-thalassemia precl...

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Autores principales: Parisi, Sarah, Finelli, Carlo, Fazio, Antonietta, De Stefano, Alessia, Mongiorgi, Sara, Ratti, Stefano, Cappellini, Alessandra, Billi, Anna Maria, Cocco, Lucio, Follo, Matilde Y., Manzoli, Lucia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830211/
https://www.ncbi.nlm.nih.gov/pubmed/33467674
http://dx.doi.org/10.3390/ijms22020827
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author Parisi, Sarah
Finelli, Carlo
Fazio, Antonietta
De Stefano, Alessia
Mongiorgi, Sara
Ratti, Stefano
Cappellini, Alessandra
Billi, Anna Maria
Cocco, Lucio
Follo, Matilde Y.
Manzoli, Lucia
author_facet Parisi, Sarah
Finelli, Carlo
Fazio, Antonietta
De Stefano, Alessia
Mongiorgi, Sara
Ratti, Stefano
Cappellini, Alessandra
Billi, Anna Maria
Cocco, Lucio
Follo, Matilde Y.
Manzoli, Lucia
author_sort Parisi, Sarah
collection PubMed
description Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and β-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or β-thalassemia preclinical and clinical studies are now based on their regulation. Among others, the main pathways involved are those regulated by transforming growth factor (TGF)-β, which negatively regulates erythrocyte differentiation and maturation, and erythropoietin (EPO), which acts on the early-stage erythropoiesis. Also small mother against decapentaplegic (SMAD) signaling molecules play a role in pathology, and activin receptor ligand traps are being investigated for future clinical applications. Even inositide-dependent signaling, which is important in the regulation of cell proliferation and differentiation, is specifically associated with erythropoiesis, with phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K) as key players that are becoming increasingly important as new promising therapeutic targets. Additionally, Roxadustat, a new erythropoiesis stimulating agent targeting hypoxia inducible factor (HIF), is under clinical development. Here, we review the role and function of the above-mentioned signaling pathways, and we describe the state of the art and new perspectives of erythropoiesis regulation in MDS and β-thalassemia.
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spelling pubmed-78302112021-01-26 Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia Parisi, Sarah Finelli, Carlo Fazio, Antonietta De Stefano, Alessia Mongiorgi, Sara Ratti, Stefano Cappellini, Alessandra Billi, Anna Maria Cocco, Lucio Follo, Matilde Y. Manzoli, Lucia Int J Mol Sci Review Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and β-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or β-thalassemia preclinical and clinical studies are now based on their regulation. Among others, the main pathways involved are those regulated by transforming growth factor (TGF)-β, which negatively regulates erythrocyte differentiation and maturation, and erythropoietin (EPO), which acts on the early-stage erythropoiesis. Also small mother against decapentaplegic (SMAD) signaling molecules play a role in pathology, and activin receptor ligand traps are being investigated for future clinical applications. Even inositide-dependent signaling, which is important in the regulation of cell proliferation and differentiation, is specifically associated with erythropoiesis, with phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K) as key players that are becoming increasingly important as new promising therapeutic targets. Additionally, Roxadustat, a new erythropoiesis stimulating agent targeting hypoxia inducible factor (HIF), is under clinical development. Here, we review the role and function of the above-mentioned signaling pathways, and we describe the state of the art and new perspectives of erythropoiesis regulation in MDS and β-thalassemia. MDPI 2021-01-15 /pmc/articles/PMC7830211/ /pubmed/33467674 http://dx.doi.org/10.3390/ijms22020827 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Parisi, Sarah
Finelli, Carlo
Fazio, Antonietta
De Stefano, Alessia
Mongiorgi, Sara
Ratti, Stefano
Cappellini, Alessandra
Billi, Anna Maria
Cocco, Lucio
Follo, Matilde Y.
Manzoli, Lucia
Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia
title Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia
title_full Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia
title_fullStr Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia
title_full_unstemmed Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia
title_short Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia
title_sort clinical and molecular insights in erythropoiesis regulation of signal transduction pathways in myelodysplastic syndromes and β-thalassemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830211/
https://www.ncbi.nlm.nih.gov/pubmed/33467674
http://dx.doi.org/10.3390/ijms22020827
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