title: Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia.
abstract: BACKGROUND
  The impact of FMS-like tyrosine kinase 3 (FLT3) mutations and mutation burden among cytogenetic subgroups of patients with acute myeloid leukemia (AML) other than normal karyotype (NK) AML is unclear.
  
  
  METHODS
  Patients with newly diagnosed AML were divided among 3 cytogenetic subgroups: core binding factor (CBF) AML, NK-AML, and poor-risk AML.
  
  
  RESULTS
  In total, 481 patients were included: 13% had, CBF-AML, 57% had NK-AML, and 30% had poor risk AML, and the frequency of any FLT3 mutations was 20%, 32%, and 7.6% in the respective cytogenetic subgroups. FLT3 mutation did not have an impact on event-free survival (EFS) in patients with CBF-AML (P = .84) and poor-risk AML (P = .37). In patients with NK-AML, EFS was worse in the FLT3-internal tandem duplication (ITD) group (20 weeks vs 41 weeks; P < .00,001) but not in the FLT3-tyrosine kinase domain (TKD) point mutation group (61 weeks vs 41 weeks; P = .15). Worse EFS and overall survival (OS) were observed among patients with NK-AML and higher FLT3-ITD burden but not among patients with FLT3-TKD mutation. In multivariate analysis, FLT3-ITD mutation was prognostic of EFS in patients with NK-AML (hazard ratio, 3.1; P = .03).
  
  
  CONCLUSIONS
  FLT3 mutations did not have a prognostic impact in patients with AML who had good-risk and poor-risk karyotypes. In patients with NK-AML, FLT3-ITD mutations led to worse survival, which was even worse among patients who had high mutation burden.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Fabio P S
authors.initials: FP
authors.lastname: Santos
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Elihu E
authors.initials: EE
authors.lastname: Estey
authors.forename: Dushyant
authors.initials: D
authors.lastname: Verma
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D050660:Core Binding Factors / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D050660:Core Binding Factors; D005819:Genetic Markers; D051941:fms-Like Tyrosine Kinase 3