SF3B1 Mutation Identifies a Distinct Subset of Myelodysplastic Syndrome With Ring Sideroblasts

Blood. 2015 Jul 9;126(2):233-41. doi: 10.1182/blood-2015-03-633537. Epub 2015 May 8.

Abstract

Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). A high prevalence of somatic mutations of SF3B1 was reported in these conditions. To identify mutation patterns that affect disease phenotype and clinical outcome, we performed a comprehensive mutation analysis in 293 patients with myeloid neoplasm and 1% or more ring sideroblasts. SF3B1 mutations were detected in 129 of 159 cases (81%) of RARS or RCMD-RS. Among other patients with ring sideroblasts, lower prevalence of SF3B1 mutations and higher prevalence of mutations in other splicing factor genes were observed (P < .001). In multivariable analyses, patients with SF3B1 mutations showed significantly better overall survival (hazard ratio [HR], .37; P = .003) and lower cumulative incidence of disease progression (HR = 0.31; P = .018) compared with SF3B1-unmutated cases. The independent prognostic value of SF3B1 mutation was retained in MDS without excess blasts, as well as in sideroblastic categories (RARS and RCMD-RS). Among SF3B1-mutated patients, coexisting mutations in DNA methylation genes were associated with multilineage dysplasia (P = .015) but had no effect on clinical outcome. TP53 mutations were frequently detected in patients without SF3B1 mutation, and were associated with poor outcome. Thus, SF3B1 mutation identifies a distinct MDS subtype that is unlikely to develop detrimental subclonal mutations and is characterized by indolent clinical course and favorable outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Sideroblastic / diagnosis
  • Anemia, Sideroblastic / epidemiology
  • Anemia, Sideroblastic / genetics*
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Myelodysplastic Syndromes / classification*
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / epidemiology
  • Myelodysplastic Syndromes / genetics*
  • Phosphoproteins / genetics*
  • Prognosis
  • RNA Splicing Factors
  • Ribonucleoprotein, U2 Small Nuclear / genetics*
  • Young Adult

Substances

  • Phosphoproteins
  • RNA Splicing Factors
  • Ribonucleoprotein, U2 Small Nuclear
  • SF3B1 protein, human