PUBLICATION

Nucleophosmin leukemogenic mutant activates Wnt signaling during zebrafish development

Authors
Barbieri, E., Deflorian, G., Pezzimenti, F., Valli, D., Saia, M., Meani, N., Gruszka, A.M., Alcalay, M.
ID
ZDB-PUB-160804-4
Date
2016
Source
Oncotarget   7(34): 55302-55312 (Journal)
Registered Authors
Deflorian, Gianluca, Pezzimenti, Federica
Keywords
Wnt signaling, acute myeloid leukemia, nucleophosmin, primitive hematopoiesis, zebrafish
MeSH Terms
  • Axin Protein/analysis
  • Zebrafish/embryology*
  • Hematopoietic Stem Cells/physiology
  • Animals
  • Wnt Signaling Pathway/physiology*
  • Mutation
  • Nuclear Proteins/genetics
  • Nuclear Proteins/physiology*
  • Leukemia, Myeloid, Acute/etiology
  • Leukemia, Myeloid, Acute/genetics*
(all 10)
PubMed
27486814 Full text @ Oncotarget
Abstract
Nucleophosmin (NPM1) is a ubiquitous multifunctional phosphoprotein with both oncogenic and tumor suppressor functions. Mutations of the NPM1 gene are the most frequent genetic alterations in acute myeloid leukemia (AML) and result in the expression of a mutant protein with aberrant cytoplasmic localization, NPMc+. Although NPMc+ causes myeloproliferation and AML in animal models, its mechanism of action remains largely unknown. Here we report that NPMc+ activates canonical Wnt signaling during the early phases of zebrafish development and determines a Wnt-dependent increase in the number of progenitor cells during primitive hematopoiesis. Coherently, the canonical Wnt pathway is active in AML blasts bearing NPMc+ and depletion of the mutant protein in the patient derived OCI-AML3 cell line leads to a decrease in the levels of active β-catenin and of Wnt target genes. Our results reveal a novel function of NPMc+ and provide insight into the molecular pathogenesis of AML bearing NPM1 mutations.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
i114TgTransgenic Insertion
    sd2TgTransgenic Insertion
      w25TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        Sequence Targeting Reagents
        No data available
        Fish
        Fish
        TU
        w25Tg
        1 - 2 of 2
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        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        DsRedEFGDsRed
        GFPEFGGFP
        1 - 2 of 2
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        Mapping
        No data available
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        Citation
        Barbieri, E., Deflorian, G., Pezzimenti, F., Valli, D., Saia, M., Meani, N., Gruszka, A.M., Alcalay, M. (2016) Nucleophosmin leukemogenic mutant activates Wnt signaling during zebrafish development. Oncotarget. 7(34):55302-55312.