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- Title
Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a retrospective study from the European APL Group.
- Authors
Callens, C.; Chevret, S.; Cayuela, J.-M.; Cassinat, B.; Raffoux, E.; de Botton, S.; Thomas, X.; Guerci, A.; Fegueux, N.; Pigneux, A.; Stoppa, A.-M.; Lamy, T.; Rigal-Huguet, F.; Vekhoff, A.; Meyer-Monard, S.; Ferrand, A.; Sanz, M.; Chomienne, C.; Fenaux, P.; Dombret, H.
- Abstract
Internal tandem duplications (ITDs) of the FLT3 gene have been observed in about 35% of APL cases. If FLT3-ITD is associated with a worse outcome in patients with acute myeloid leukemia (AML) in general, its prognostic value in acute promyelocytic leukemia (APL) is still a matter of debate. We investigated incidence, associated clinical features, and prognostic implication of FLT3-ITD, but also FLT3-D835 point mutation and N-Ras or K-Ras mutations in 119 APL patients, all prospectively enrolled in the two consecutive APL-93 and APL-2000 trials. Mutation incidences were 38, 20, and 4%, for FLT3-ITD, FLT3-D835, and Ras, respectively. The presence of FLT3-ITD was associated with high white blood cell count, high Sanz index, M3-variant subtype, and V/S PML-RARα isoforms. Complete remission (CR), induction death, and death in CR rates were not affected by FLT3 or Ras mutations, as well as cumulative incidence of relapse. However, a trend for a shorter overall survival (P=0.09) was observed in FLT3-ITD patients, because of a very poor postrelapse survival (P=0.02). This feature, which has been also reported in patients with AML in general, is suggestive of an underlying genetic instability in FLT3-ITD patients, leading to the acquisition of additional unknown bad-prognosis gene mutations at relapse.Leukemia (2005) 19, 1153–1160. doi:10.1038/sj.leu.2403790 Published online 12 May 2005
- Subjects
ACUTE myeloid leukemia; LEUKEMIA; LEUCOCYTES; GENETIC mutation; BLOOD cell count; BLOOD diseases
- Publication
Leukemia (08876924), 2005, Vol 19, Issue 7, p1153
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/sj.leu.2403790