title: Impact of numerical variation in FMS-like tyrosine kinase receptor 3 internal tandem duplications on clinical outcome in normal karyotype acute myelogenous leukemia.
abstract: BACKGROUND
  The impact of single versus multiple fms-like tyrosine kinase receptor 3 internal tandem duplication (FLT3-ITD) mutations on the clinical outcome of patients with acute myelogenous leukemia has not been well studied, and particularly has not been investigated while simultaneously accounting for the quantitative mutation burden.
  
  
  METHODS
  The authors conducted a multivariate analysis of overall survival, event-free survival, and complete remission duration, including numeric variation (single vs multiple) and quantitative mutant burden of FLT3-ITD as variables among other clinically relevant factors.
  
  
  RESULTS
  An analysis of a cohort of 1043 patients with AML demonstrated that, among patients with normal-karyotype acute myelogenous leukemia and FLT3-ITD mutation, overall survival and event-free survival were not affected by the number of FLT3-ITD mutations, but complete remission duration was significantly longer in patients who had multiple FLT3-ITD mutations (median, 86 weeks vs 34 weeks; P = .03).
  
  
  CONCLUSIONS
  The current results indicated that time-to-event analyses of patients with normal-karyotype acute myelogenous leukemia and FLT3-ITD mutation should take into account the number of mutations and the mutant burden, among other factors.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. gborthak@mdanderson.org
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3