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The Genetics of Myelodysplastic Syndromes: Clinical Relevance

Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of geneti...

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Autores principales: Chiereghin, Chiara, Travaglino, Erica, Zampini, Matteo, Saba, Elena, Saitta, Claudia, Riva, Elena, Bersanelli, Matteo, Della Porta, Matteo Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392119/
https://www.ncbi.nlm.nih.gov/pubmed/34440317
http://dx.doi.org/10.3390/genes12081144
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author Chiereghin, Chiara
Travaglino, Erica
Zampini, Matteo
Saba, Elena
Saitta, Claudia
Riva, Elena
Bersanelli, Matteo
Della Porta, Matteo Giovanni
author_facet Chiereghin, Chiara
Travaglino, Erica
Zampini, Matteo
Saba, Elena
Saitta, Claudia
Riva, Elena
Bersanelli, Matteo
Della Porta, Matteo Giovanni
author_sort Chiereghin, Chiara
collection PubMed
description Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of genetic mutations that results in heterogeneous clinical phenotype and outcome. Genetic studies have enabled the identification of a set of recurrently mutated genes which are central to the pathogenesis of MDS and can be organized into a limited number of cellular pathways, including RNA splicing (SF3B1, SRSF2, ZRSR2, U2AF1 genes), DNA methylation (TET2, DNMT3A, IDH1/2), transcription regulation (RUNX1), signal transduction (CBL, RAS), DNA repair (TP53), chromatin modification (ASXL1, EZH2), and cohesin complex (STAG2). Few genes are consistently mutated in >10% of patients, whereas a long tail of 40–50 genes are mutated in <5% of cases. At diagnosis, the majority of MDS patients have 2–4 driver mutations and hundreds of background mutations. Reliable genotype/phenotype relationships were described in MDS: SF3B1 mutations are associated with the presence of ring sideroblasts and more recent studies indicate that other splicing mutations (SRSF2, U2AF1) may identify distinct disease categories with specific hematological features. Moreover, gene mutations have been shown to influence the probability of survival and risk of disease progression and mutational status may add significant information to currently available prognostic tools. For instance, SF3B1 mutations are predictors of favourable prognosis, while driver mutations of other genes (such as ASXL1, SRSF2, RUNX1, TP53) are associated with a reduced probability of survival and increased risk of disease progression. In this article, we review the most recent advances in our understanding of the genetic basis of myelodysplastic syndromes and discuss its clinical relevance.
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spelling pubmed-83921192021-08-28 The Genetics of Myelodysplastic Syndromes: Clinical Relevance Chiereghin, Chiara Travaglino, Erica Zampini, Matteo Saba, Elena Saitta, Claudia Riva, Elena Bersanelli, Matteo Della Porta, Matteo Giovanni Genes (Basel) Review Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of genetic mutations that results in heterogeneous clinical phenotype and outcome. Genetic studies have enabled the identification of a set of recurrently mutated genes which are central to the pathogenesis of MDS and can be organized into a limited number of cellular pathways, including RNA splicing (SF3B1, SRSF2, ZRSR2, U2AF1 genes), DNA methylation (TET2, DNMT3A, IDH1/2), transcription regulation (RUNX1), signal transduction (CBL, RAS), DNA repair (TP53), chromatin modification (ASXL1, EZH2), and cohesin complex (STAG2). Few genes are consistently mutated in >10% of patients, whereas a long tail of 40–50 genes are mutated in <5% of cases. At diagnosis, the majority of MDS patients have 2–4 driver mutations and hundreds of background mutations. Reliable genotype/phenotype relationships were described in MDS: SF3B1 mutations are associated with the presence of ring sideroblasts and more recent studies indicate that other splicing mutations (SRSF2, U2AF1) may identify distinct disease categories with specific hematological features. Moreover, gene mutations have been shown to influence the probability of survival and risk of disease progression and mutational status may add significant information to currently available prognostic tools. For instance, SF3B1 mutations are predictors of favourable prognosis, while driver mutations of other genes (such as ASXL1, SRSF2, RUNX1, TP53) are associated with a reduced probability of survival and increased risk of disease progression. In this article, we review the most recent advances in our understanding of the genetic basis of myelodysplastic syndromes and discuss its clinical relevance. MDPI 2021-07-27 /pmc/articles/PMC8392119/ /pubmed/34440317 http://dx.doi.org/10.3390/genes12081144 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chiereghin, Chiara
Travaglino, Erica
Zampini, Matteo
Saba, Elena
Saitta, Claudia
Riva, Elena
Bersanelli, Matteo
Della Porta, Matteo Giovanni
The Genetics of Myelodysplastic Syndromes: Clinical Relevance
title The Genetics of Myelodysplastic Syndromes: Clinical Relevance
title_full The Genetics of Myelodysplastic Syndromes: Clinical Relevance
title_fullStr The Genetics of Myelodysplastic Syndromes: Clinical Relevance
title_full_unstemmed The Genetics of Myelodysplastic Syndromes: Clinical Relevance
title_short The Genetics of Myelodysplastic Syndromes: Clinical Relevance
title_sort genetics of myelodysplastic syndromes: clinical relevance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392119/
https://www.ncbi.nlm.nih.gov/pubmed/34440317
http://dx.doi.org/10.3390/genes12081144
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