Genes, Vol. 12, Pages 1144: The Genetics of Myelodysplastic Syndromes: Clinical Relevance

Genes, Vol. 12, Pages 1144: The Genetics of Myelodysplastic Syndromes: Clinical Relevance Genes doi: 10.3390/genes12081144 Authors: Chiara Chiereghin Erica Travaglino Matteo Zampini Elena Saba Claudia Saitta Elena Riva Matteo Bersanelli Matteo Giovanni Della Porta 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 ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research