title: The prognostic significance of IDH2 mutations in AML depends on the location of the mutation.
abstract: We have investigated the prognostic significance of isocitrate dehydrogenase 2 (IDH2) mutations in 1473 younger adult acute myeloid leukemia patients treated in 2 United Kingdom Medical Research Council trials. An IDH2 mutation was present in 148 cases (10%), 80% at R140 and 20% at R172. Patient characteristics and outcome differed markedly between the 2 mutations. IDH2(R140) significantly correlated with nucleophosmin mutations (NPM1(MUT)), whereas IDH2(R172) cases generally lacked other molecular mutations. An IDH2(R140) mutation was an independent favorable prognostic factor for relapse (P = .004) and overall survival (P = .008), and there was no significant heterogeneity with regard to NPM1 or FLT3 internal tandem duplication (FLT3/ITD) genotype. Relapse in FLT3/ITD(WT)NPM1(MUT)IDH2(R140) patients was lower than in favorable-risk cytogenetics patients in the same cohort (20% and 38% at 5 years, respectively). The presence of an IDH2(R172) mutation was associated with a significantly worse outcome than IDH2(R140), and relapse in FLT3/ITD(WT)NPM1(WT)IDH2(R172) patients was comparable with adverse-risk cytogenetics patients (76% and 72%, respectively).
authors: Department of Haematology, UCL Cancer Institute, London, United Kingdom.
authors: Claire L
authors: CL
authors: Green
authors: Catherine M
authors: CM
authors: Evans
authors: Lu
authors: L
authors: Zhao
authors: Robert K
authors: RK
authors: Hills
authors: Alan K
authors: AK
authors: Burnett
authors: David C
authors: DC
authors: Linch
authors: Rosemary E
authors: RE
authors: Gale