title: Nucleophosmin gene mutations in acute myeloid leukemia.
abstract: BACKGROUND
  Heterozygous mutation of the nucleophosmin gene (NPM1) has recently been described as one of the most frequent genetic lesions in acute myeloid leukemia (AML).
  
  
  OBJECTIVE
  (1) To discuss the clinical, morphologic, immunophenotypic, and genetic features of AML with NPM1 gene mutations, along with various detection methods, (2) To explore the mechanisms by which NPM1 gene mutations contribute to leukemogenesis. DATA SOURCES/EXTRACTION: Data were analyzed from 7 recently published papers.
  
  
  RESULTS
  NPM1 gene mutations tend to occur more frequently in women, and also tend to be associated with a higher white blood cell count. There is no significant age difference. NPM1-mutated AML is preferentially associated with AML with monocytic differentiation (in particular FAB M5b), lack of CD34, normal cytogenetics, FLT3 gene mutations, and a trend toward favorable clinical outcome, especially in patients without FLT3 gene mutation. NPM1 gene mutations cause a frame shift in the C-terminus of exon 12, disrupting the NPM nucleolar-localization signal or generating a leucine-rich nuclear export motif, resulting in abnormal cytoplasmic accumulation of NPM. Several methods are suitable for detecting NPM1 gene mutation, including molecular and immunohistochemical studies. These mutations may contribute to leukemogenesis, at least in part, through disruption of the p14(ARF) (alternative reading frame) MDM2-p53 pathway and centrosomal duplication.
  
  
  CONCLUSIONS
  Detection of NPM1 gene mutations may allow dissection of the heterogeneous group of AML with normal karyotype into prognostically different subgroups. Exploring the mechanisms may lead to a better understanding of how mutant NPM protein becomes leukemogenic, thereby providing insights for the development of new chemotherapeutic agents.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 72, Houston, TX 77030, USA. weinachen@mdanderson.org
authors.forename: Weina
authors.initials: W
authors.lastname: Chen
authors.forename: Georgios Z
authors.initials: GZ
authors.lastname: Rassidakis
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D020732:Cytogenetic Analysis; D005821:Genetic Techniques; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008206:Lymphatic Diseases / Q000235:genetics; D008967:Molecular Biology; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D014178:Translocation, Genetic
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin