title: Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.
abstract: Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.
authors.affiliation: Centro Ricerca Tettamanti, Clinica Pediatrica University of Milano-Bicocca, Ospedale San Gerardo, 20052 Monza, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Dell'Oro
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giarin
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rossi
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000737:chemistry; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin