title: Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem duplication.
abstract: OBJECTIVE
  The biological characteristics and the prognostic significance of the internal tandem duplication of the FLT3 (FLT3/ITD) were investigated in a series of de novo acute myeloid leukemia (AML) patients. One hundred and fifty-six adult patients with AML were included in the study. FLT3/ITD was detected in 41 (26%) patients (FLT3/ITD(+)).
  
  
  METHODS
  The main differences observed between the groups with and without FLT3/ITD: a higher leukocyte count, a raised percentage of a normal karyotype and a more frequent M5 FAB diagnosis in the FLT3/ITD(+) patients. As regards the immunophenotype characteristics the FLT3/ITD(+) group very often expressed monocytic markers (CD36 and CD11b) and less commonly immature markers (CD34 and CD117). A promyelocytic-like immunophenotype pattern was also detected in a minority of these patients(4/36).
  
  
  RESULTS
  The FLT3/ITD(+) patients had a shorter overall survival, a shorter event-free survival and a higher probability of relapse. Minimal residual disease (MRD) was investigated in the FLT3/ITD(+) patients using flow cytometry. This technique had a sensitivity of 62% and a specificity of 83% in relapse prediction. Minimal residual disease analysis was hampered by the low number of patients with detectable aberrant immunophenotype.
  
  
  CONCLUSIONS
  A high frequency of changes in the phenotype and/or genotype pattern between diagnosis and relapse was detected (5/6). FLT3/ITD is a frequent molecular lesion in de novo adult AML and seems to be associated with a monocytic differentiation, a high leukocyte count and a poor prognosis. Immunophenotype and genotype patterns observed at relapse suggest that the FLT3/ITD(+) blasts may be genetically unstable and prone to clonal evolution. FLT3/ITD may not be a suitable target for minimal residual disease studies.
authors.affiliation: Laboratori d'Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Luz
authors.initials: L
authors.lastname: Muñoz
authors.forename: Ana
authors.initials: A
authors.lastname: Aventín
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Jordi
authors.initials: J
authors.lastname: Juncà
authors.forename: Gemma
authors.initials: G
authors.lastname: Acebedo
authors.forename: Alicia
authors.initials: A
authors.lastname: Domingo
authors.forename: María
authors.initials: M
authors.lastname: Rozman
authors.forename: J Pio
authors.initials: JP
authors.lastname: Torres
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.forename: Josep F
authors.initials: JF
authors.lastname: Nomdedéu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D015703:Antigens, CD; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3