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Leukemia. 2006 Jun;20(6):965-70.
Incidence and prognostic impact of
c-Kit, FLT3, and Ras gene mutations in core binding
factor acute myeloid leukemia (CBF-AML).
Boissel N,
Leroy H, Brethon B, Philippe N, de Botton S,
Auvrignon A, Raffoux E, Leblanc T, Thomas X, Hermine
O, Quesnel B, Baruchel A, Leverger G, Dombret H,
Preudhomme C; Acute Leukemia French Association
(ALFA); Leucemies Aigues Myeloblastiques de l'Enfant
(LAME) Cooperative Groups.
Service d'Hematologie Adulte, Hopital Saint-Louis,
Paris, France.
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.
PMID: 16598313 [PubMed - indexed for
MEDLINE]