title: Lower frequency of NPM1 and FLT3-ITD mutations in a South African adult de novo AML cohort.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hemopoietic progenitor cells diagnosed in individuals of any age, but with a median age of 67 years at presentation in adults. Assessment of the mutation status of nucleophosmin protein-1 (NPM1) and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is essential for the prognosis, and treatment of AML.
  
  
  METHODS
  A total of 160 de novo AML cases, both cytogenetically normal and abnormal, were analyzed for the presence of NPM1 and FLT3-ITD mutations, and the results assessed in conjunction with epidemiological, clinical, and laboratory findings.
  
  
  RESULTS
  Nucleophosmin protein-1 mutations were found in 7.5%, while FLT3-ITD was present in 12% of these cases. Both of these were lower than expected. The median age at diagnosis of AML was 41 years, and for the FLT3-ITD only cases, median age was 33 years; these ages were younger than expected.
  
  
  CONCLUSIONS
  The lower reported frequencies and younger median age at diagnosis of AML and these specific mutations may be contributed to by a number of factors including effects of race on age of presentation, inclusion of patients diagnosed with de novo AML only, and a generally younger median age of the South African population.
authors.affiliation: National Health Laboratory Services, Johannesburg, South Africa; Department of Molecular Medicine and Haematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: R C
authors.initials: RC
authors.lastname: Marshall
authors.forename: A
authors.initials: A
authors.lastname: Tlagadi
authors.forename: M
authors.initials: M
authors.lastname: Bronze
authors.forename: V
authors.initials: V
authors.lastname: Kana
authors.forename: S
authors.initials: S
authors.lastname: Naidoo
authors.forename: T M
authors.initials: TM
authors.lastname: Wiggill
authors.forename: S C
authors.initials: SC
authors.lastname: Carmona
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D017434:Protein Structure, Tertiary; D013019:South Africa; D016019:Survival Analysis; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; FLT3-ITD; NPM1; South Africa; frequency