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

被引:273
作者
Alcalay, M
Tiacci, E
Bergomas, R
Bigerna, B
Venturini, E
Minardi, SP
Meani, N
Diverio, D
Bernard, L
Tizzoni, L
Volorio, S
Luzi, L
Colombo, E
Lo Coco, F
Mecucci, C
Falini, B
Pelicci, PG
机构
[1] IFOM, Inst Mol Oncol, Italian Fdn Canc Res, I-20139 Milan, Italy
[2] Univ Perugia, Inst Hematol, I-06100 Perugia, Italy
[3] European Inst Oncol, Milan, Italy
[4] Univ Roma La Sapienza, Inst Hematol, Rome, Italy
[5] Univ Roma Tor Vergata, Dept Biopathol, Rome, Italy
关键词
D O I
10.1182/blood-2005-02-0560
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 hernatopoietic progenitor.
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收藏
页码:899 / 902
页数:4
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