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

Myriam Alcalay, Enrico Tiacci, Roberta Bergomas, Barbara Bigerna, Elisa Venturini, Simone P. Minardi, Natalia Meani, Daniela Diverio, Loris Bernard, Laura Tizzoni, Sara Volorio, Lucilla Luzi, Emanuela Colombo, Francesco Lo Coco, Cristina Mecucci, Brunangelo Falini, Pier Giuseppe Pelicci

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)899-902
Number of pages4
JournalBlood
Volume106
Issue number3
DOIs
Publication statusPublished - Aug 1 2005

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ASJC Scopus subject areas

  • Hematology

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