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.
| Original language | English |
|---|---|
| Pages (from-to) | 254-266 |
| Number of pages | 13 |
| Journal | New England Journal of Medicine |
| Volume | 352 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jan 20 2005 |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
Cite this
Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. / Falini, Brunangelo; Mecucci, Cristina; 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.
In: New England Journal of Medicine, Vol. 352, No. 3, 20.01.2005, p. 254-266.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype
AU - Falini, Brunangelo
AU - Mecucci, Cristina
AU - Tiacci, Enrico
AU - Alcalay, Myriam
AU - Rosati, Roberto
AU - Pasqualucci, Laura
AU - La Starza, Roberta
AU - Diverio, Daniela
AU - Colombo, Emanuela
AU - Santucci, Antonella
AU - Bigerna, Barbara
AU - Pacini, Roberta
AU - Pucciarini, Alessandra
AU - Liso, Arcangelo
AU - Vignetti, Marco
AU - Fazi, Paola
AU - Meani, Natalia
AU - Pettirossi, Valentina
AU - Saglio, Giuseppe
AU - Mandelli, Franco
AU - Lo-Coco, Francesco
AU - Pelicci, Pier Giuseppe
AU - Martelli, Massimo F.
PY - 2005/1/20
Y1 - 2005/1/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=19944427850&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=19944427850&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa041974
DO - 10.1056/NEJMoa041974
M3 - Article
C2 - 15659725
AN - SCOPUS:19944427850
VL - 352
SP - 254
EP - 266
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 3
ER -