Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling in acute myeloid leukemia with mutated NPM


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, Fms-like tyrosine kinase (FLT3) mutations and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 with non-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. 78 de novo AMLs, negative for AML-associated chromosomal translocations at the cytogenetic and/or molecular level.

ORGANISM(S): Homo sapiens

SUBMITTER: Myriam Alcalay 

PROVIDER: E-GEOD-34860 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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.

Alcalay Myriam M   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  

Blood 20050414 3


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 wi  ...[more]

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