SF3B1 mutations in patients with myelodysplastic syndromes: the mutation is stable during disease evolution

Am J Hematol. 2014 Aug;89(8):E109-15. doi: 10.1002/ajh.23734. Epub 2014 Apr 28.

Abstract

The SF3B1 mutation can be detected in patients with myelodysplastic syndrome (MDS), but the report regarding the association of this mutation with other genetic alterations and its stability during disease progression is limited. In this study, SF3B1 mutations were identified in 10% of total cohort of 479 MDS patients and 61.8% of 34 patients with refractory anemia with ring sideroblasts (RARS). SF3B1 mutations were closely associated with older age, higher platelet counts, lower lactate dehydrogenase levels, good-risk cytogenetics, and mutations of DNMT3A, but inversely related to ASXL1 mutations. Most SF3B1-mutated patients had concurrent other genetic alterations, including DNMT3A and RUNX1 mutations. There was no prognostic difference between patients with SF3B1 mutations and those without. Sequential studies in 417 samples from 142 patients demonstrated that all SF3B1-mutated patients retained the same mutations during disease evolution with the exception of two patients who lost the mutation after allogeneic hematopoietic stem cell transplantation, whereas none of the SF3B1-wild patients acquired a novel mutation during clinical follow-ups. In conclusion, the patients with SF3B1 mutations had distinct clinic-biologic features. SF3B1 mutations, accompanied with other genetic alterations, especially DNMT3A mutations, may play a role in the development of MDS, but have little role in disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anemia, Refractory, with Excess of Blasts / genetics*
  • Anemia, Refractory, with Excess of Blasts / metabolism
  • Anemia, Refractory, with Excess of Blasts / pathology
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • Disease Progression
  • Female
  • Humans
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Middle Aged
  • Mutation Rate*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • RNA Splicing Factors
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Ribonucleoprotein, U2 Small Nuclear / genetics*
  • Ribonucleoprotein, U2 Small Nuclear / metabolism

Substances

  • ASXL1 protein, human
  • Core Binding Factor Alpha 2 Subunit
  • DNMT3A protein, human
  • Phosphoproteins
  • RNA Splicing Factors
  • RUNX1 protein, human
  • Repressor Proteins
  • Ribonucleoprotein, U2 Small Nuclear
  • SF3B1 protein, human
  • L-Lactate Dehydrogenase
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A