Nucleophosmin leukemogenic mutant activates Wnt signaling during zebrafish development

Elisa Barbieri, Gianluca Deflorian, Federica Pezzimenti, Debora Valli, Marco Saia, Natalia Meani, Alicja M. Gruszka, Myriam Alcalay

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 Wntdependent 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.

Original languageEnglish
Pages (from-to)55302-55312
Number of pages11
JournalOncotarget
Volume7
Issue number34
DOIs
Publication statusPublished - 2016

Fingerprint

Zebrafish
Acute Myeloid Leukemia
Mutant Proteins
Catenins
Mutation
Wnt Signaling Pathway
Phosphoproteins
Hematopoiesis
Genes
Stem Cells
Animal Models
Cell Line
nucleophosmin
Neoplasms

Keywords

  • Acute myeloid leukemia
  • Nucleophosmin
  • Primitive hematopoiesis
  • Wnt signaling
  • Zebrafish

ASJC Scopus subject areas

  • Oncology

Cite this

Nucleophosmin leukemogenic mutant activates Wnt signaling during zebrafish development. / Barbieri, Elisa; Deflorian, Gianluca; Pezzimenti, Federica; Valli, Debora; Saia, Marco; Meani, Natalia; Gruszka, Alicja M.; Alcalay, Myriam.

In: Oncotarget, Vol. 7, No. 34, 2016, p. 55302-55312.

Research output: Contribution to journalArticle

Barbieri, Elisa ; Deflorian, Gianluca ; Pezzimenti, Federica ; Valli, Debora ; Saia, Marco ; Meani, Natalia ; Gruszka, Alicja M. ; Alcalay, Myriam. / Nucleophosmin leukemogenic mutant activates Wnt signaling during zebrafish development. In: Oncotarget. 2016 ; Vol. 7, No. 34. pp. 55302-55312.
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AU - Saia, Marco

AU - Meani, Natalia

AU - Gruszka, Alicja M.

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