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.
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.
Alcalay
Myriam
M
IFOM-IEO Campus, Via Adamello 16, 20139, Milan, Italy. myriam.alcalay@ifom-ieo-campus.it
Tiacci
Enrico
E
Bergomas
Roberta
R
Bigerna
Barbara
B
Venturini
Elisa
E
Minardi
Simone P
SP
Meani
Natalia
N
Diverio
Daniela
D
Bernard
Loris
L
Tizzoni
Laura
L
Volorio
Sara
S
Luzi
Lucilla
L
Colombo
Emanuela
E
Lo Coco
Francesco
F
Mecucci
Cristina
C
Falini
Brunangelo
B
Pelicci
Pier Giuseppe
PG
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
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D000090243:Nucleophosmin; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3