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Review

The Genetics of Myelodysplastic Syndromes: Clinical Relevance

1
IRCCS Humanitas Research Hospital, Via Alessandro Manzoni 56, 20089 Rozzano, Italy
2
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Italy
*
Author to whom correspondence should be addressed.
Genes 2021, 12(8), 1144; https://doi.org/10.3390/genes12081144
Submission received: 20 May 2021 / Revised: 5 July 2021 / Accepted: 22 July 2021 / Published: 27 July 2021
(This article belongs to the Special Issue Genetics and Genomics of Blood Disorders)

Abstract

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.
Keywords: myelodysplastic syndrome; gene mutations; disease classification; prognosis myelodysplastic syndrome; gene mutations; disease classification; prognosis

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MDPI and ACS Style

Chiereghin, C.; Travaglino, E.; Zampini, M.; Saba, E.; Saitta, C.; Riva, E.; Bersanelli, M.; Della Porta, M.G. The Genetics of Myelodysplastic Syndromes: Clinical Relevance. Genes 2021, 12, 1144. https://doi.org/10.3390/genes12081144

AMA Style

Chiereghin C, Travaglino E, Zampini M, Saba E, Saitta C, Riva E, Bersanelli M, Della Porta MG. The Genetics of Myelodysplastic Syndromes: Clinical Relevance. Genes. 2021; 12(8):1144. https://doi.org/10.3390/genes12081144

Chicago/Turabian Style

Chiereghin, Chiara, Erica Travaglino, Matteo Zampini, Elena Saba, Claudia Saitta, Elena Riva, Matteo Bersanelli, and Matteo Giovanni Della Porta. 2021. "The Genetics of Myelodysplastic Syndromes: Clinical Relevance" Genes 12, no. 8: 1144. https://doi.org/10.3390/genes12081144

APA Style

Chiereghin, C., Travaglino, E., Zampini, M., Saba, E., Saitta, C., Riva, E., Bersanelli, M., & Della Porta, M. G. (2021). The Genetics of Myelodysplastic Syndromes: Clinical Relevance. Genes, 12(8), 1144. https://doi.org/10.3390/genes12081144

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