title: Mutations in the isocitrate dehydrogenase 2 gene and IDH1 SNP 105C > T have a prognostic value in acute myeloid leukemia.
abstract: BACKGROUND
  The isocitrate dehydrogenase (IDH1/IDH2) genes are metabolic enzymes, which are frequently mutated in acute myeloid leukemia (AML). The enzymes acquire neomorphic enzymatic activity when they mutated.
  
  
  METHODS
  We have investigated the frequency and outcome of the acquired IDH1/IDH2 mutations and the IDH1 SNP 105C > T (rs11554137) in 189 unselected de novo AML patients by polymerase chain reaction amplification followed by direct sequencing. The survival are presented in Kaplan Meier curves with log rank test. Multivariable survival analysis was conducted using Cox regression method, taking age, risk group, treatment, IDH1/2 mutations and IDH1 SNP105 genotype into account.
  
  
  RESULTS
  Overall, IDH1/2 mutations were found in 41/187 (21.7%) of the AML patients. IDH1 codon 132 mutations were present in 7.9%, whereas IDH2 mutations were more frequent and mutations were identified in codon 140 and 172 in a frequency of 11.1% and 2.6%, respectively. The SNP 105C > T was present in 10.5% 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 < 0.001) was observed in the intermediate risk patient group. 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 AML patients (p = 0.004).
  
  
  CONCLUSIONS
  Our results indicate that AML-patients with IDH2 mutations or the IDH1 SNP 105C > T variant can represent a new subgroup for risk stratification and may indicate new treatment options.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden ; Department of Hematology, County Council of Östergötland, Linköping, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Willander
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Ingrid Jakobsen
authors.initials: IJ
authors.lastname: Falk
authors.affiliation: Department of Hematology, County Council of Östergötland, Linköping, Sweden.
authors.forename: Roza
authors.initials: R
authors.lastname: Chaireti
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Esbjörn
authors.initials: E
authors.lastname: Paul
authors.affiliation: Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Monica
authors.initials: M
authors.lastname: Hermansson
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden ; Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Gréen
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden ; Department of Hematology, County Council of Östergötland, Linköping, Sweden.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Lotfi
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden ; Department of Clinical Genetics, County Council of Östergötland, Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Söderkvist
keywords: AML; IDH1; IDH2; Prognostic markers; SNP