title: Detection of CD34, TdT, CD56, CD2, CD4, and CD14 by flow cytometry is associated with NPM1 and FLT3 mutation status in cytogenetically normal acute myeloid leukemia.
abstract: In 83 patients with cytogenetically normal acute myeloid leukemia (CN-AML), those with NPM1 and wild-type FLT3 (FLT3-wt) mutation and their poor prognostic combination had distinctive flow cytometric findings: CN-AML with a mutation of NPM1 (NPMI-Mt) were CD34(-), CD14(-), and CD2pos and CD4; those with FLT3-internal tandem duplications (ITD) were CD56pos, those with NPM1-Mt and FLT3-wt were CD34(-) and CD56(-); and those with poor prognostic combination NPM1-wt and FLT3-ITD were CD34pos and TdTpos.
  
  
  METHODS
  We retrospectively correlated NPM1 and FLT3 mutation status with flow cytometric profile of leukemic blasts in 83 adult patients with cytogenetically normal acute myeloid leukemia (CN-AML).
  
  
  RESULTS
  Mutation of the NPM1 gene (NPM1.mt) was found in 39 (47%) of 83 patients, and internal tandem duplication (ITD) of the FLT3 gene (FLT3-ITD) was seen in 38 (46%) of 83 patients. Patients with CN-AML and with NPM1.mt were less likely to express CD34 (33% vs. 93%; 2P = .0001), CD2 (0% vs. 14%; 2P = .0187), and CD14 (6% vs. 22%, 2P = .0476), and were more likely to express CD4 (65.5% vs. 37%; 2P = .0367) and CD19 (49% vs. 27%; 2P = .0506). The patients with CN-AML and with FLT3-ITD were more likely to express CD56 (47% vs. 23%; 2P = .0393). Moreover, patients with favorable prognostic combination of NPM1.mt and wild-type (wt) FLT3 (n = 18) were less likely to express CD34 (33% vs. 74% all others; 2P = .0021) and CD56 (6% vs. 37% all others; 2P = .0072). The group with an unfavorable prognostic combination of NPM1-wt and FLT3-ITD (n = 17) were more likely to express CD34 (88% vs. 45% all others; 2P = .0011) and TdT (40% vs. 2% all others; 2P = .0054).
  
  
  CONCLUSIONS
  In patients with CN-AML, characteristic flow cytometric profile is associated with NPM1 and FLT3 mutation status.
authors.affiliation: Division of Laboratory Haematology, Vancouver General Hospital, Vancouver, British Columbia, Canada. bakul.dalal@vch.ca
authors.forename: Bakul I
authors.initials: BI
authors.lastname: Dalal
authors.forename: Soudeh
authors.initials: S
authors.lastname: Mansoor
authors.forename: Mita
authors.initials: M
authors.lastname: Manna
authors.forename: Steven
authors.initials: S
authors.lastname: Pi
authors.forename: Giovanna Di
authors.initials: GD
authors.lastname: Sauro
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hogge
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology*; D003582:Cytogenetics; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3