Details

Autor(en) / Beteiligte

• Chiereghin, Chiara
• Travaglino, Erica
• Zampini, Matteo
• Saba, Elena
• Saitta, Claudia
• Riva, Elena
• Bersanelli, Matteo
• Della Porta, Matteo Giovanni

Titel

The Genetics of Myelodysplastic Syndromes: Clinical Relevance

Ist Teil von

• Genes, 2021-07, Vol.12 (8), p.1144

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 ( , , , genes), DNA methylation ( , , ), transcription regulation ( ), signal transduction ( , ), DNA repair ( ), chromatin modification ( , ), and cohesin complex ( ). 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: mutations are associated with the presence of ring sideroblasts and more recent studies indicate that other splicing mutations ( , ) 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, mutations are predictors of favourable prognosis, while driver mutations of other genes (such as , , , ) 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.