1. Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a retrospective study from the European APL Group.
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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., and Dombret, H.
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ACUTE myeloid leukemia ,LEUKEMIA ,LEUCOCYTES ,GENETIC mutation ,BLOOD cell count ,BLOOD diseases - 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 [ABSTRACT FROM AUTHOR]
- Published
- 2005
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