title: Biological and clinical consequences of NPM1 mutations in AML.
abstract: Acute myeloid leukemia (AML) is characterized by accumulation of myeloid cells in the bone marrow because of impaired differentiation and proliferation, resulting in hematopoietic insufficiency. NPM1 is one of the most commonly mutated genes in AML, present in 20-30% of cases. Mutations in NPM1 represent a distinct entity in the World Health Organization (WHO) classification and commonly indicate a better risk prognosis. In this review, we discuss the many functions of NPM1, the consequence of mutations in NPM1 and possible mechanisms through which mutations lead to leukemogenesis. We also discuss clinical consequences of mutations, associated gene expression patterns and the role of NPM1 mutations in informing prognosis and therapeutic decisions and predicting relapse in AML.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Ontario, Canada.
authors.forename: E M
authors.initials: EM
authors.lastname: Heath
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: S M
authors.initials: SM
authors.lastname: Chan
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Ontario, Canada.
authors.forename: M D
authors.initials: MD
authors.lastname: Minden
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Ontario, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Murphy
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: L I
authors.initials: LI
authors.lastname: Shlush
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Ontario, Canada.
authors.forename: A D
authors.initials: AD
authors.lastname: Schimmer
mesh_terms: D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D000066491:Clinical Decision-Making; D004843:Epistasis, Genetic; D015973:Gene Expression Regulation, Leukemic; D005787:Gene Frequency; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D011379:Prognosis; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin