Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML)

Leukemia. 2006 Jun;20(6):965-70. doi: 10.1038/sj.leu.2404188.


In core binding factors (CBF) acute myeloid leukemia (AML), the disruption of CBFalpha/beta genes impairs normal hematopoietic differentiation and is supposed to cooperate with additional mutations promoting proliferation. The incidence and the prognosis of receptor tyrosine kinase (RTK) c-Kit and FLT3 mutations and Ras mutations were evaluated in 103 pediatric and adult patients with CBF-AML. c-Kit mutations were present in 17% patients. c-Kit exon 8 mutations were more frequent in inv(16) than in t(8;21) subset (20 versus 6%). Only one patient had FLT3-ITD but FLT3-D835 was as frequent as reported in AML population (7%). Ras mutations were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%, P=0.001). RTK mutations were associated with a higher white blood cell count (WBC) (36 versus 21 G/L, P=0.05). FLT3 mutations were significantly associated with a shorter EFS and survival (P<0.0001 and P=0.0002) owing to an excess of early events. c-Kit mutations were associated with a shorter EFS and RFS (P=0.002 and P=0.003) in t(8;21) but not inv(16) patients. As previously observed, Ras mutations did not affect prognosis. Screening for RTK mutations may help to identify patients with a more adverse outcome and thus susceptible to benefit from intensified protocols or RTK inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Core Binding Factors / genetics*
  • Exons
  • Female
  • Humans
  • Infant
  • Leukemia, Myeloid / diagnosis
  • Leukemia, Myeloid / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Proto-Oncogene Proteins c-kit / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retrospective Studies
  • Survival Rate
  • fms-Like Tyrosine Kinase 3 / genetics*


  • Core Binding Factors
  • FLT3 protein, human
  • Proto-Oncogene Proteins c-kit
  • fms-Like Tyrosine Kinase 3
  • Proto-Oncogene Proteins p21(ras)