Mutations in the isocitrate dehydrogenase 1/2 genes and IDH1 SNP 105C>T have a prognostic value in acute myeloid leukemia

The isocitrate dehydrogenase (IDH1/IDH2) genes are frequently mutated and reported to associate with poor prognosis in acute myeloid leukemia (AML). We have investigated the frequency and outcome of the acquired IDH1/IDH2 mutations and the IDH1 SNP 105C>T (rs11554137) in 207 unselected de novo AML patients. IDH1 codon 132 mutations were present in 7.7%, whereas IDH2 mutations were more frequent and mutations were identified in codon 140 and 172 in a frequency of 10.1% and 2.9%, respectively. The SNP 105C>T was present in 10.1% of the patients, similar to the normal population. A significantly reduced overall survival (OS) for patients carrying IDH2 codon 140 mutation compared with patients carrying wild-type IDH2 gene (p=0.009) was observed in the intermediate risk patient group with cytogenetically normal karyotype (CN-AML). Neither in the entire patient group nor subdivided in different risk groups, IDH1 mutations had any significance on OS compared to the wild-type IDH1 patients. A significant difference in OS between the heterozygous SNP variant and the homozygous wild-type was observed in the intermediate risk FLT3 negative CN-AML, (p=0.007). Our results indicate that IDH2 mutations and the IDH1 SNP 105C>T variant may represent a new subgroup for risk stratification and may indicate new treatment options.