title: Prevalence and Clinical Effect of IDH1 and IDH2 Mutations Among Cytogenetically Normal Acute Myeloid Leukemia Patients.
abstract: BACKGROUND
  The frequencies of isocitrate dehydrogenase (IDH) 1 and IDH2 mutations among patients with de novo acute myeloid leukemia (AML) are different among different ethnic groups. The aim of this study was to determine the frequencies of IDH1 and IDH2 mutations among Egyptian AML patients and its effect on patient outcomes.
  
  
  METHODS
  This study was conducted in 211 adult patients (104 men; 107 women; age range, 18-68 years) with cytogenetically normal AML. DNA was extracted from bone marrow samples at the time of diagnosis. The exon 4 of IDH1 and IDH2 were amplified using polymerase chain reaction and sequenced for detection of mutations.
  
  
  RESULTS
  IDH1 mutations were detected in 18 of 211 AML patients (8.5%) in the form of 8 cases, R132H; 6 cases, R132C; 2 cases, R132S; 1 case, R132G; and 1 case, R132V mutations). IDH2 mutations were detected in 22 of 211 AML patients (10.4%) in the form of 20 cases, R140Q; and 2 cases, R172K mutations. The overall survival after correction for nucleophosmin 1 and fims- related tyrosine kinase internal tandem duplication was significantly shorter in AML patients with the IDH mutation compared with those with wild type (P = .02).
  
  
  CONCLUSIONS
  IDH1 and IDH2 mutations are negative prognostic markers in AML patients. A novel mutation (R132V) was detected in IDH1 in our cohort of AML patients. We recommend molecular testing for IDH1 and IDH2 mutations for proper risk stratification of AML patients before the start of therapy.
authors.affiliation: Hematology Unit, Clinical Pathology Department, Mansoura University, Mansoura, Egypt. Electronic address: salaharef@yahoo.com.
authors.forename: Salah
authors.initials: S
authors.lastname: Aref
authors.affiliation: Faculty of Science, Mansoura University, Mansoura, Egypt.
authors.forename: El Sayed
authors.initials: el S
authors.lastname: Kamel Areida
authors.affiliation: Faculty of Science, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed Fathy
authors.initials: MF
authors.lastname: Abdel Aaal
authors.affiliation: Faculty of Science, Mansoura University, Mansoura, Egypt.
authors.forename: Ola Mohamed
authors.initials: OM
authors.lastname: Adam
authors.affiliation: Hematology Unit, Clinical Pathology Department, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed Sabry
authors.initials: MS
authors.lastname: El-Ghonemy
authors.affiliation: Medical Oncology Unit, Mansoura University Oncology Center, Mansoura Faculty of Medicine, Mansoura, Egypt.
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: El-Baiomy
authors.affiliation: Clinical Hematology Unit, Mansoura University Oncology Center, Mansoura Faculty of Medicine, Mansoura, Egypt.
authors.forename: Tarek Abou
authors.initials: TA
authors.lastname: Zeid
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D015995:Prevalence; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: AML; IDH; Mutation; Prognosis