title: Correlation analysis of p53 protein isoforms with NPM1/FLT3 mutations and therapy response in acute myeloid leukemia.
abstract: The wild-type tumor-suppressor gene TP53 encodes several isoforms of the p53 protein. However, while the role of p53 in controlling normal cell cycle progression and tumor suppression is well established, the clinical significance of p53 isoform expression is unknown. A novel bioinformatic analysis of p53 isoform expression in 68 patients with acute myeloid leukemia revealed distinct p53 protein biosignatures correlating with clinical outcome. Furthermore, we show that mutated FLT3, a prognostic marker for short survival in AML, is associated with expression of full-length p53. In contrast, mutated NPM1, a prognostic marker for long-term survival, correlated with p53 isoforms β and γ expression. In conclusion, p53 biosignatures contain useful information for cancer evaluation and prognostication.
authors.affiliation: Hematology Section, Institute of Medicine, University of Bergen, Bergen, Norway.
authors.forename: N
authors.initials: N
authors.lastname: Ånensen
authors.forename: S M
authors.initials: SM
authors.lastname: Hjelle
authors.forename: W
authors.initials: W
authors.lastname: Van Belle
authors.forename: I
authors.initials: I
authors.lastname: Haaland
authors.forename: E
authors.initials: E
authors.lastname: Silden
authors.forename: J-C
authors.initials: JC
authors.lastname: Bourdon
authors.forename: R
authors.initials: R
authors.lastname: Hovland
authors.forename: K
authors.initials: K
authors.lastname: Taskén
authors.forename: S
authors.initials: S
authors.lastname: Knappskog
authors.forename: P E
authors.initials: PE
authors.lastname: Lønning
authors.forename: Ø
authors.initials: Ø
authors.lastname: Bruserud
authors.forename: B T
authors.initials: BT
authors.lastname: Gjertsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D020033:Protein Isoforms / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3