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NIPBL: a new player in myeloid cell differentiation
The nucleophosmin 1 gene (NPM1) is the most frequently mutated gene in acute myeloid leukemia. Notably, NPM1 mutations are always accompanied by additional mutations such as those in cohesin genes RAD21, SMC1A, SMC3, and STAG2 but not in the cohesin regulator, nipped B-like (NIPBL). In this work, we...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ferrata Storti Foundation
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601076/ https://www.ncbi.nlm.nih.gov/pubmed/30630974 http://dx.doi.org/10.3324/haematol.2018.200899 |
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author | Mazzola, Mara Deflorian, Gianluca Pezzotta, Alex Ferrari, Laura Fazio, Grazia Bresciani, Erica Saitta, Claudia Ferrari, Luca Fumagalli, Monica Parma, Matteo Marasca, Federica Bodega, Beatrice Riva, Paola Cotelli, Franco Biondi, Andrea Marozzi, Anna Cazzaniga, Gianni Pistocchi, Anna |
author_facet | Mazzola, Mara Deflorian, Gianluca Pezzotta, Alex Ferrari, Laura Fazio, Grazia Bresciani, Erica Saitta, Claudia Ferrari, Luca Fumagalli, Monica Parma, Matteo Marasca, Federica Bodega, Beatrice Riva, Paola Cotelli, Franco Biondi, Andrea Marozzi, Anna Cazzaniga, Gianni Pistocchi, Anna |
author_sort | Mazzola, Mara |
collection | PubMed |
description | The nucleophosmin 1 gene (NPM1) is the most frequently mutated gene in acute myeloid leukemia. Notably, NPM1 mutations are always accompanied by additional mutations such as those in cohesin genes RAD21, SMC1A, SMC3, and STAG2 but not in the cohesin regulator, nipped B-like (NIPBL). In this work, we analyzed a cohort of adult patients with acute myeloid leukemia and NPM1 mutation and observed a specific reduction in the expression of NIPBL but not in other cohesin genes. In our zebrafish model, overexpression of the mutated form of NPM1 also induced downregulation of nipblb, the zebrafish ortholog of human NIPBL. To investigate the hematopoietic phenotype and the interaction between mutated NPM1 and nipblb, we generated a zebrafish model with nipblb downregulation which showed an increased number of myeloid progenitors. This phenotype was due to hyper-activation of the canonical Wnt pathway: myeloid cells blocked in an undifferentiated state could be rescued when the Wnt pathway was inhibited by dkk1b mRNA injection or indomethacin administration. Our results reveal, for the first time, a role for NIPBL during zebrafish hematopoiesis and suggest that an interplay between NIPBL/NPM1 may regulate myeloid differentiation in zebrafish and humans through the canonical Wnt pathway and that dysregulation of these interactions may drive leukemic transformation. |
format | Online Article Text |
id | pubmed-6601076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-66010762019-07-08 NIPBL: a new player in myeloid cell differentiation Mazzola, Mara Deflorian, Gianluca Pezzotta, Alex Ferrari, Laura Fazio, Grazia Bresciani, Erica Saitta, Claudia Ferrari, Luca Fumagalli, Monica Parma, Matteo Marasca, Federica Bodega, Beatrice Riva, Paola Cotelli, Franco Biondi, Andrea Marozzi, Anna Cazzaniga, Gianni Pistocchi, Anna Haematologica Article The nucleophosmin 1 gene (NPM1) is the most frequently mutated gene in acute myeloid leukemia. Notably, NPM1 mutations are always accompanied by additional mutations such as those in cohesin genes RAD21, SMC1A, SMC3, and STAG2 but not in the cohesin regulator, nipped B-like (NIPBL). In this work, we analyzed a cohort of adult patients with acute myeloid leukemia and NPM1 mutation and observed a specific reduction in the expression of NIPBL but not in other cohesin genes. In our zebrafish model, overexpression of the mutated form of NPM1 also induced downregulation of nipblb, the zebrafish ortholog of human NIPBL. To investigate the hematopoietic phenotype and the interaction between mutated NPM1 and nipblb, we generated a zebrafish model with nipblb downregulation which showed an increased number of myeloid progenitors. This phenotype was due to hyper-activation of the canonical Wnt pathway: myeloid cells blocked in an undifferentiated state could be rescued when the Wnt pathway was inhibited by dkk1b mRNA injection or indomethacin administration. Our results reveal, for the first time, a role for NIPBL during zebrafish hematopoiesis and suggest that an interplay between NIPBL/NPM1 may regulate myeloid differentiation in zebrafish and humans through the canonical Wnt pathway and that dysregulation of these interactions may drive leukemic transformation. Ferrata Storti Foundation 2019-07 /pmc/articles/PMC6601076/ /pubmed/30630974 http://dx.doi.org/10.3324/haematol.2018.200899 Text en Copyright© 2019 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Article Mazzola, Mara Deflorian, Gianluca Pezzotta, Alex Ferrari, Laura Fazio, Grazia Bresciani, Erica Saitta, Claudia Ferrari, Luca Fumagalli, Monica Parma, Matteo Marasca, Federica Bodega, Beatrice Riva, Paola Cotelli, Franco Biondi, Andrea Marozzi, Anna Cazzaniga, Gianni Pistocchi, Anna NIPBL: a new player in myeloid cell differentiation |
title | NIPBL: a new player in myeloid cell differentiation |
title_full | NIPBL: a new player in myeloid cell differentiation |
title_fullStr | NIPBL: a new player in myeloid cell differentiation |
title_full_unstemmed | NIPBL: a new player in myeloid cell differentiation |
title_short | NIPBL: a new player in myeloid cell differentiation |
title_sort | nipbl: a new player in myeloid cell differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601076/ https://www.ncbi.nlm.nih.gov/pubmed/30630974 http://dx.doi.org/10.3324/haematol.2018.200899 |
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