title: Recent advances in the understanding of myelodysplastic syndromes with ring sideroblasts.
abstract: Myeloid neoplasms with ring sideroblasts are currently categorized within the myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the World Health Organization classification. Recent findings have identified that the presence of ring sideroblasts in these disorders has a unique molecular basis, i.e., the somatic mutation of SF3B1, a gene encoding a splicing factor. Mutations of SF3B1 occur in up to 90% of patients with refractory anaemia with unilineage dysplasia (RARS) and 70% of those with refractory cytopenia with multilineage dysplasia and ring sideroblasts or RARS associated with marked thrombocytosis. Experimental evidence has shown that mutant SF3B1 results in the abnormal splicing of several genes, primarily due to misrecognition of 3' splice sites. The resulting aberrant mRNAs undergo nonsense-mediated mRNA decay (NMD), resulting in haploinsufficiency of canonical transcripts and protein expression. In addition, it is also possible that NMD-insensitive aberrant transcripts are translated into proteins with altered function. Patients with MDS carrying the SF3B1 mutation show a homogeneous disease phenotype characterized by isolated erythroid dysplasia and mild dysplasia in granulocytic or megakaryocytic lineages, supporting the notion that the SF3B1 mutation identifies a distinct entity within MDS. The available evidence suggests that these findings may have relevant impact on the diagnosis, classification and management of patients with these neoplasms.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.|Department of Haematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Malcovati
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.|Department of Haematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000756:Anemia, Sideroblastic / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D015672:Erythroid Precursor Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000209:etiology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D012326:RNA Splicing; D000072260:RNA Splicing Factors / Q000235:genetics
chemical_list: D010750:Phosphoproteins; D000072260:RNA Splicing Factors; C112491:SF3B1 protein, human; D007501:Iron
keywords: RNA splicing; SF3B1 mutation; myelodysplastic syndrome; ring sideroblasts; sideroblastic anaemia