title: Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.
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.
authors.affiliation: Institute of Hematology, University of Perugia, Perugia, Italy. faliniem@unipg.it
authors.forename: Brunangelo
authors.initials: B
authors.lastname: Falini
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Enrico
authors.initials: E
authors.lastname: Tiacci
authors.forename: Myriam
authors.initials: M
authors.lastname: Alcalay
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosati
authors.forename: Laura
authors.initials: L
authors.lastname: Pasqualucci
authors.forename: Roberta
authors.initials: R
authors.lastname: La Starza
authors.forename: Daniela
authors.initials: D
authors.lastname: Diverio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colombo
authors.forename: Antonella
authors.initials: A
authors.lastname: Santucci
authors.forename: Barbara
authors.initials: B
authors.lastname: Bigerna
authors.forename: Roberta
authors.initials: R
authors.lastname: Pacini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pucciarini
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Liso
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Paola
authors.initials: P
authors.lastname: Fazi
authors.forename: Natalia
authors.initials: N
authors.lastname: Meani
authors.forename: Valentina
authors.initials: V
authors.lastname: Pettirossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: Pier-Giuseppe
authors.initials: PG
authors.lastname: Pelicci
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin