title: WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia.
abstract: We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracycline-AraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 (p = 0.0001). Multivariate analysis of 81 patients with intermediate karyotype revealed that younger age (p = 0.00009), NPM gene mutation (p = 0.002), and WT1 >75th percentile (>2365) (p = 0.003) were independent, positive factors for complete remission (CR). WT1 expression above 2365 was correlated also to longer event-free survival (EFS) and overall survival (OS) in the same subset of patients (p = 0.003 and p = 0.02, respectively); the same finding occurred in younger patients with AML with intermediate karyotype (p = 0.008 and p = 0.01, respectively). In patients with intermediate karyotype, FLT3 internal tandem duplication (ITD) negatively affected EFS (EFS at 30 months: 30% vs. 6% in FLT3-ITD negative and FLT3 positive patients, respectively; p = 0.01) and OS (OS at 30 months: 38% vs. 20%, p = 0.03). The positive prognostic value of high WT1 expression does not have a clear explanation; it may be implicated either with WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on the leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy.
authors.affiliation: Department of Hematology and Oncology, Azienda Ospedaliera Universitaria San Martino, Genova, Italy. ematlab@unige.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Miglino
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.forename: Gianmatteo
authors.initials: G
authors.lastname: Pica
authors.forename: Raffaella
authors.initials: R
authors.lastname: Grasso
authors.forename: Marino
authors.initials: M
authors.lastname: Clavio
authors.forename: Micaela
authors.initials: M
authors.lastname: Bergamaschi
authors.forename: Filippo
authors.initials: F
authors.lastname: Ballerini
authors.forename: Anna
authors.initials: A
authors.lastname: Ghiso
authors.forename: Chiara
authors.initials: C
authors.lastname: Ghiggi
authors.forename: Laura
authors.initials: L
authors.lastname: Mitscheunig
authors.forename: Germana
authors.initials: G
authors.lastname: Beltrami
authors.forename: Antonia
authors.initials: A
authors.lastname: Cagnetta
authors.forename: Luana
authors.initials: L
authors.lastname: Vignolo
authors.forename: Maria Vita
authors.initials: MV
authors.lastname: Lucchetti
authors.forename: Sara
authors.initials: S
authors.lastname: Aquino
authors.forename: Ivana
authors.initials: I
authors.lastname: Pierri
authors.forename: Mario
authors.initials: M
authors.lastname: Sessarego
authors.forename: Angelo Michele
authors.initials: AM
authors.lastname: Carella
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003561:Cytarabine / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D000090243:Nucleophosmin; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000032:analysis / Q000235:genetics*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000032:analysis / Q000235:genetics
chemical_list: C442828:BAALC protein, human; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D025721:WT1 Proteins; D003561:Cytarabine; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3