title: Patient-specific analysis of  FLT3 internal tandem duplications for the prognostication and monitoring of acute myeloid leukemia.
abstract: OBJECTIVE
  Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 ( FLT3) gene occur in 13-35% of patients with acute myeloid leukemia (AML). FLT3-ITD is associated with poor clinical outcome and is an indication for allogeneic stem cell transplantation (allo-SCT).
  
  
  METHODS
  To investigate FLT3-ITD length, position, and mutational load in AML cases, we developed patient-specific quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assays and correlated the results with established sensitive minimal residual disease (MRD) parameters and clinical outcome.
  
  
  RESULTS
  In 409 patients with AML, FLT3-ITDs could be detected in 54 cases (13%). Within our cohort, patients with FLT3-ITD ≥ 45 base pairs had significantly higher relapse rates (P = 0.03) and a worse overall survival (P = 0.03). Our method could be applied to 97% of FLT3-ITD-positive patients and was as sensitive as other MRD parameters such as PML-RARA , NPM1 mutations, or MLL -PTD (correlation: r = 0.63; 0.99, and 0.99, respectively). MRD negativity predicted lasting remission independent of allo-SCT (N = 7) or non-allo-SCT (N = 9). All paired diagnostic/relapsed samples showed FLT3-ITD positivity. Compared with bone marrow samples, FLT3-ITD analyses appeared to be equivalently sensitive in peripheral blood.
  
  
  CONCLUSIONS
  We conclude that individualized monitoring of FLT3-ITD in patients with AML may guide treatment decisions and should be evaluated for the indication for allo-SCT.
authors.affiliation: Department I of Internal Medicine, University at Cologne, Cologne, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Schiller
authors.forename: Inka
authors.initials: I
authors.lastname: Praulich
authors.forename: Cristiano
authors.initials: C
authors.lastname: Krings Rocha
authors.forename: Karl-Anton
authors.initials: KA
authors.lastname: Kreuzer
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D000090243:Nucleophosmin; D011379:Prognosis; D012189:Retrospective Studies; D020080:Tandem Repeat Sequences; D014184:Transplantation, Homologous; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3