title: Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis.
abstract: BACKGROUND
  Nucleophosmin (NPM1) gene mutations are reported to predict a favorable prognosis in acute myeloid leukemia (AML) patients. Aberrant cytoplasmic localization of nucleophosmin (NPM) protein is reported be a surrogate for NPM1 gene mutation.
  
  
  METHODS
  Using immunohistochemical (IHC) analysis, we assessed for NPM (clone 376) expression in formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. DNA sequencing of exon 12 of NPM1 gene was performed in 104 patients.
  
  
  RESULTS
  The study included 252 AML patients: 192 de novo AML, 33 AML preceded by either myelodysplastic syndrome or chronic myelomonocytic leukemia, and 27 therapy-related AML. The median age was 62 years and 115 patients were <or=60 years old. All patients received intensive chemotherapy. Cytoplasmic NPM was detected in 59 of 252 (23%) patients, including 48 of 192 (25%) de novo AML and 33 of 94 (35%) with a normal karyotype. DNA sequencing identified NPM1 mutations in 30 of 38 cases with cytoplasmic NPM and 10 of 66 cases with nuclear NPM. Cytoplasmic NPM was associated with young patient age (P=.024), FLT3/ITD (P=.005), CD34 negative blasts (P<.001), high peripheral blood blast count (P=.041), and high serum albumin level (P=.028). No statistical differences in overall or event-free survival were found on the basis of NPM localization. Similar results were obtained in patients<or=60 years old with normal karyotype and wild-type FLT3 (P=.768).
  
  
  CONCLUSIONS
  IHC assessment for NPM localization did not predict prognosis in this patient cohort. The discordance between immunohistochemistry and DNA sequencing results indicates that DNA sequencing cannot be replaced by IHC assessment.
authors.affiliation: Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. skonople@mdanderson.org
authors.forename: Sergej
authors.initials: S
authors.lastname: Konoplev
authors.forename: Xuelin
authors.initials: X
authors.lastname: Huang
authors.forename: Harry A
authors.initials: HA
authors.lastname: Drabkin
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Weina
authors.initials: W
authors.lastname: Chen
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin