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

• Published in: Blood 2005-08, Vol.106 (3), p.899-902
• Main Authors: Alcalay, Myriam, Tiacci, Enrico, Bergomas, Roberta, Bigerna, Barbara, Venturini, Elisa, Minardi, Simone P., Meani, Natalia, Diverio, Daniela, Bernard, Loris, Tizzoni, Laura, Volorio, Sara, Luzi, Lucilla, Colombo, Emanuela, Lo Coco, Francesco, Mecucci, Cristina, Falini, Brunangelo, Pelicci, Pier Giuseppe
• Format: Article
• Language: English
• Subjects: Acute Disease; Biological and medical sciences; Cell Lineage; Cytoplasm - chemistry; DNA Mutational Analysis; fms-Like Tyrosine Kinase 3; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells; Leukemia, Myeloid - classification; Leukemia, Myeloid - genetics; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Neoplasm Proteins - analysis; Nuclear Proteins - analysis; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Proto-Oncogene Proteins - genetics; Receptor Protein-Tyrosine Kinases - genetics; Up-Regulation - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-02-0560

Approximately one third of acute myeloid leukemias (AML55553) 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.