title: Minimal residual disease detection in acute myeloid leukemia by mutant nucleophosmin (NPM1): comparison with WT1 gene expression.
abstract: BACKGROUND
  Molecular analysis of minimal residual disease is only applicable in acute myeloblastic leukemia (AML) patients with genetic markers (20-30%). This study analyzes the feasibility of the real-time quantitative polymerase chain reaction (RQ-PCR) assay to detect mutant nucleophosmin (NPM1) during follow-up in AML patients. Moreover, we compare the NPM1 results with those of WT1 expression to MRD assessment.
  
  
  METHODS
  The study includes 97 samples from 24 AML patients with type A NPM1 mutation at diagnosis. MRD was evaluated simultaneous by RQ-PCR assay to detect NPM1-mutated and WT1 expression.
  
  
  RESULTS
  The expression levels of WT1 and NPM1 in 93 paired samples showed a strong positive correlation (r=0.81; p<0.0001). However, the kinetics of disappearance were different, WT1 decreased rapidly after induction but maintained these residual levels after treatment in patients in complete remission, whereas NPM1 experienced a mild reduction after induction but was undetectable in long survivor patients.
  
  
  CONCLUSIONS
  This study shows the feasibility of the RQ-PCR assay to monitor MRD in AML patients carrying NPM1 mutations and its advantage over RQ-PCR assay for WT1. Owing to NPM1-mutated is specific of leukemic cells and shows higher levels at presentation.
authors.affiliation: Department of Medical Pathology, Hospital Universitario La Fe Valencia, Spain. barragan_eva@gva.es
authors.forename: Eva
authors.initials: E
authors.lastname: Barragan
authors.forename: Juan C
authors.initials: JC
authors.lastname: Pajuelo
authors.forename: Sandra
authors.initials: S
authors.lastname: Ballester
authors.forename: Oscar
authors.initials: O
authors.lastname: Fuster
authors.forename: Jose
authors.initials: J
authors.lastname: Cervera
authors.forename: Federico
authors.initials: F
authors.lastname: Moscardo
authors.forename: Leonor
authors.initials: L
authors.lastname: Senent
authors.forename: Esperanza
authors.initials: E
authors.lastname: Such
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Pascual
authors.initials: P
authors.lastname: Bolufer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D016162:Genes, Wilms Tumor; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction / Q000379:methods; D012008:Recurrence; D012074:Remission Induction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin