Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.
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.
Falini
Brunangelo
B
Institute of Hematology, University of Perugia, Perugia, Italy. faliniem@unipg.it
Mecucci
Cristina
C
Tiacci
Enrico
E
Alcalay
Myriam
M
Rosati
Roberto
R
Pasqualucci
Laura
L
La Starza
Roberta
R
Diverio
Daniela
D
Colombo
Emanuela
E
Santucci
Antonella
A
Bigerna
Barbara
B
Pacini
Roberta
R
Pucciarini
Alessandra
A
Liso
Arcangelo
A
Vignetti
Marco
M
Fazi
Paola
P
Meani
Natalia
N
Pettirossi
Valentina
V
Saglio
Giuseppe
G
Mandelli
Franco
F
Lo-Coco
Francesco
F
Pelicci
Pier-Giuseppe
PG
Martelli
Massimo F
MF
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D002466:Cell Nucleolus; D003593:Cytoplasm / Q000737:chemistry*; D004252:DNA Mutational Analysis; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D000090243:Nucleophosmin; D012074:Remission Induction; D014162:Transfection; D014178:Translocation, Genetic
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin