Clinical implications of the SETBP1 mutation in patients with primary myelodysplastic syndrome and its stability during disease progression

Am J Hematol. 2014 Feb;89(2):181-6. doi: 10.1002/ajh.23611. Epub 2013 Nov 20.


Mutations of the SET binding protein 1 (SETBP1) gene have been identified in patients with myeloid neoplasms, but the clinical relevance of this mutation and its association with other gene mutations in myelodysplastic syndrome (MDS) and the stability during disease progression remains unclear. Mutations in SETBP1 gene at exon 4 were analyzed by polymerase chain reaction and direct sequencing in 430 MDS patients. The results were correlated with clinical features, cytogenetics, gene mutations and treatment outcomes. SETBP1 mutations were identified in 14 (3.3%) of the 430 patients with primary MDS based on the FAB classification and 8 (2.4%) of the 333 patients based on the WHO classification. The SETBP1 mutation was closely associated with higher white blood cell counts, isochromosome of 17q, monosomy 7, and mutations of ASXL1, EZH2 and SRSF2. With a median follow-up of 43.9 months, MDS patients, based on either the FAB or WHO classification, had a significantly poorer overall survival (OS) if they harbored SETBP1 mutation. Further, SETBP1 mutation was an independent poor prognostic factor for OS (HR = 1.842, CI 95%, 1.1018-3.332, P = 0.043) irrespective of age, sex, and the International Prognostic Scoring System. Sequential analysis showed that the original SETBP1 mutations in the eight SETBP1-mutated patients studied were retained while two of the 101 SETBP1-wild patients acquired novel SETBP1 mutations during follow-ups. The SETBP1 mutation is associated with poor prognosis in MDS. The mutation can be acquired during the clinical course suggesting it may play a role in disease progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Substitution
  • Carrier Proteins / genetics*
  • Chromosome Aberrations
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Karyotype
  • Male
  • Middle Aged
  • Mutation*
  • Myelodysplastic Syndromes / diagnosis*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Nuclear Proteins / genetics*
  • Patient Outcome Assessment
  • Prognosis
  • Young Adult


  • Carrier Proteins
  • Nuclear Proteins
  • SETBP1 protein, human