title: [FLT3 and NPM1 gene mutations in patients with acute myeloid leukemias and the impact of FLT3-ITD mutations on the survival of patients with a normal karyotype].
abstract: OBJECTIVE
  To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML).
  
  
  METHODS
  The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied.
  
  
  RESULTS
  Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1 and FLT3-ITD+/ NPM-T genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-1TD mutation on EFS.
  
  
  CONCLUSIONS
  The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM-genotypes to be identified as a poor prognosis group.
authors.forename: I S
authors.initials: IS
authors.lastname: Martynkevich
authors.forename: S V
authors.initials: SV
authors.lastname: Gritsaev
authors.forename: M V
authors.initials: MV
authors.lastname: Moskalenko
authors.forename: M P
authors.initials: MP
authors.lastname: Ivanova
authors.forename: V Iu
authors.initials: VIu
authors.lastname: Aksenova
authors.forename: S A
authors.initials: SA
authors.lastname: Tiranova
authors.forename: K M
authors.initials: KM
authors.lastname: Abdulkadyrov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004247:DNA / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012426:Russia / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D004247:DNA; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3