title: Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance.
abstract: Approximately one third of acute myeloid leukemias (AMLs) are characterized by aberrant cytoplasmic localization of nucleophosmin (NPMc+ AML), consequent to mutations in the NPM putative nucleolar localization signal. These events are mutually exclusive with the major AML-associated chromosomal rearrangements, and are frequently associated with normal karyotype, FLT3 mutations, and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 without major chromosomal abnormalities) that were characterized for the subcellular localization and mutation status of NPM. Unsupervised clustering clearly separated NPMc+ from NPMc- AMLs, regardless of the presence of FLT3 mutations or non-major chromosomal rearrangements, supporting the concept that NPMc+ AML represents a distinct entity. The molecular signature of NPMc+ AML includes up-regulation of several genes putatively involved in the maintenance of a stem-cell phenotype, suggesting that NPMc+ AML may derive from a multipotent hematopoietic progenitor.
authors.affiliation: IFOM-IEO Campus, Via Adamello 16, 20139, Milan, Italy. myriam.alcalay@ifom-ieo-campus.it
authors.forename: Myriam
authors.initials: M
authors.lastname: Alcalay
authors.forename: Enrico
authors.initials: E
authors.lastname: Tiacci
authors.forename: Roberta
authors.initials: R
authors.lastname: Bergomas
authors.forename: Barbara
authors.initials: B
authors.lastname: Bigerna
authors.forename: Elisa
authors.initials: E
authors.lastname: Venturini
authors.forename: Simone P
authors.initials: SP
authors.lastname: Minardi
authors.forename: Natalia
authors.initials: N
authors.lastname: Meani
authors.forename: Daniela
authors.initials: D
authors.lastname: Diverio
authors.forename: Loris
authors.initials: L
authors.lastname: Bernard
authors.forename: Laura
authors.initials: L
authors.lastname: Tizzoni
authors.forename: Sara
authors.initials: S
authors.lastname: Volorio
authors.forename: Lucilla
authors.initials: L
authors.lastname: Luzi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colombo
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Coco
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
mesh_terms: D000208:Acute Disease; D019070:Cell Lineage; D003593:Cytoplasm / Q000737:chemistry*; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells; D007951:Leukemia, Myeloid / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D000090243:Nucleophosmin; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3