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: Claire L Green, Catherine M Evans, Lu Zhao, Robert K Hills, Alan K Burnett, David C Linch, Rosemary E Gale
• Journal: Blood (Blood) Vol. 118 Issue 2 Pg. 409-12 (Jul 14 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21596855 (Publication Type: Evaluation Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• NPM1 protein, human
• Nucleophosmin
• IDH2 protein, human
• Isocitrate Dehydrogenase

Topics

• Adult
• Base Sequence (physiology)
• Biomarkers, Tumor (genetics, metabolism)
• Case-Control Studies
• Cohort Studies
• DNA Mutational Analysis
• Female
• Genotype
• Humans
• Isocitrate Dehydrogenase (genetics, physiology)
• Leukemia, Myeloid, Acute (diagnosis, genetics, mortality, pathology)
• Male
• Middle Aged
• Mutation (physiology)
• Nucleophosmin
• Prognosis
• Recurrence
• Survival Analysis