title: Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype.
abstract: BACKGROUND
  Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1andIDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects ofIDHmutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up.
  
  
  METHODS
  In our study samples from 110 adultde novoAML-NK were studied for the presence ofIDH1andIDH2mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse.
  
  
  RESULTS
  IDHmutations were found in 25 (23%) patients.IDH+ patients tend to have lower CR rate compared toIDH-patients (44%vs62.2%, p = 0.152), and had slightly lower disease free survival (12 monthsvs17 months; p = 0.091). On the other hand, the presence ofIDHmutations had significant impact on overall survival (2vs7 months; p = 0.039). The stability ofIDHmutations were studied sequentially in 19IDH+ patients. All of them lost the mutation in CR, and the sameIDHmutations were detected in relapsed samples.
  
  
  CONCLUSIONS
  Our study shows that the presence ofIDHmutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also,IDHmutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Marijana
authors.initials: M
authors.lastname: Virijevic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Teodora
authors.initials: T
authors.lastname: Karan-Djurasevic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Marjanovic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Tosic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Mitrovic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Djunic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Colovic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Vidovic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Nada
authors.initials: N
authors.lastname: Suvajdzic-Vukovic
authors.affiliation: Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragica
authors.initials: D
authors.lastname: Tomin
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlovic
keywords: IDH1 mutations; IDH2 mutations; acute myeloid leukaemia; normal karyotype