Recent advances in the understanding of myelodysplastic syndromes with ring sideroblasts

Research output: Contribution to journalReview article

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.

Original languageEnglish
Pages (from-to)847-858
Number of pages12
JournalBritish Journal of Haematology
Volume174
Issue number6
DOIs
Publication statusPublished - Sep 1 2016

Fingerprint

Myelodysplastic Syndromes
Nonsense Mediated mRNA Decay
Mutation
Refractory Anemia
Haploinsufficiency
Thrombocytosis
Neoplasms
RNA Splice Sites
Genes
Proteins
Phenotype
Messenger RNA

Keywords

  • myelodysplastic syndrome
  • ring sideroblasts
  • RNA splicing
  • SF3B1 mutation
  • sideroblastic anaemia

ASJC Scopus subject areas

  • Medicine(all)
  • Hematology

Cite this

Recent advances in the understanding of myelodysplastic syndromes with ring sideroblasts. / Malcovati, Luca; Cazzola, Mario.

In: British Journal of Haematology, Vol. 174, No. 6, 01.09.2016, p. 847-858.

Research output: Contribution to journalReview article

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