FLT3 and NPM1 mutations in myelodysplastic syndromes: Frequency and potential value for predicting progression to acute myeloid leukemia

Am J Clin Pathol. 2011 Jan;135(1):62-9. doi: 10.1309/AJCPEI9XU8PYBCIO.


We reviewed FLT3 and NPM1 mutation data in a large cohort of patients with myelodysplastic syndrome (MDS). The frequencies of FLT3 and NPM1 mutation were 2.0% and 4.4%, respectively, and mutations were restricted to cases of intermediate- and high-risk MDS. Cytogenetic abnormalities were identified in 46.9% of cases. FLT3 mutations were associated with a complex karyotype (P = .009), whereas NPM1 mutations were associated with a diploid karyotype (P < .001). FLT3 mutation (P < .001) was associated with progression to acute myeloid leukemia (AML), as were a higher bone marrow (BM) blast count (P < .001) and complex cytogenetics (P = .039). No patient with an NPM1 mutation alone had disease that progressed to AML. Cox proportional regression multivariate analysis indicated that FLT3 mutation, NPM1 mutation, complex cytogenetics, BM blast count, pancytopenia, and age were independent factors that correlated with progression-free survival. We conclude that FLT3 and NPM1 mutations are rare in MDS, but assessment of mutation status is potentially useful for predicting progression to AML.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow Cells / pathology
  • Chromosome Aberrations
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / pathology
  • Nuclear Proteins / genetics*
  • Nucleophosmin
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Texas / epidemiology
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*


  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3