Title: Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype
Authors: Falini, Brunangelo ×
Mecucci, Christina
Tiacci, Enrico
Alcalay, Myriam
Rosati, Roberto
Pasqualucci, Laura
La Starza, Roberta
Diverio, Daniela
Colombo, Emanuela
Santucci, Antonella
Bigerna, Barbara
Pacini, Roberta
Pucciarini, Alessandra
Liso, Arcangelo
Vignetti, Marco
Fazi, Paola
Meani, Natalia
Pettirossi, Valentina
Saglio, Giuseppe
Mandelli, Franco
Lo-Coco, Francesco
Pelicci, Pier-Giuseppe
Martelli, Massimo F #
Issue Date: Jan-2005
Series Title: New England Journal of Medicine vol:352 issue:3 pages:254-66
Abstract: BACKGROUND: Nucleophosmin (NPM), a nucleocytoplasmic shuttling protein with prominent nucleolar localization, regulates the ARF-p53 tumor-suppressor pathway. Translocations involving the NPM gene cause cytoplasmic dislocation of the NPM protein. METHODS: We used immunohistochemical methods to study the subcellular localization of NPM in bone marrow-biopsy specimens from 591 patients with primary acute myelogenous leukemia (AML). We then correlated the presence of cytoplasmic NPM with clinical and biologic features of the disease. RESULTS: Cytoplasmic NPM was detected in 208 (35.2 percent) of the 591 specimens from patients with primary AML but not in 135 secondary AML specimens or in 980 hematopoietic or extrahematopoietic neoplasms other than AML. It was associated with a wide spectrum of morphologic subtypes of the disease, a normal karyotype, and responsiveness to induction chemotherapy, but not with recurrent genetic abnormalities. There was a high frequency of FLT3 internal tandem duplications and absence of CD34 and CD133 in AML specimens with a normal karyotype and cytoplasmic dislocation of NPM, but not in those in which the protein was restricted to the nucleus. AML specimens with cytoplasmic NPM carried mutations of the NPM gene that were predicted to alter the protein at its C-terminal; this mutant gene caused cytoplasmic localization of NPM in transfected cells. CONCLUSIONS: Cytoplasmic NPM is a characteristic feature of a large subgroup of patients with AML who have a normal karyotype, NPM gene mutations, and responsiveness to induction chemotherapy.
ISSN: 0028-4793
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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