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

N. Boissel, H. Leroy, B. Brethon, N. Philippe, S. de Botton, A. Auvrignon, E. Raffoux, T. Leblanc, X. Thomas, O. Hermine, B. Quesnel, A. Baruchel, G. Leverger, H. Dombret, C. Preudhomme

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Abstract

In core binding factors (CBF) acute myeloid leukemia (AML), the disruption of CBFα/β 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.

Original languageEnglish
Pages (from-to)965-970
Number of pages6
JournalLeukemia
Volume20
Issue number6
DOIs
Publication statusPublished - 1 Jan 2006
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • Gene mutations
  • Prognosis

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