Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model
NKX2 homeobox family proteins play a role in cancer development. Molecular cloning of a translocation t(10;14)(q24;q32) from a marginal-zone B-cell lymphoma revealed NKX2-3 as an IGH partner gene, leading to increased NKX2-3 expression with respect to B lymphocytes. NKX2-3 overexpression was also de...
| Autor: | |
|---|---|
| Tipo de documento: | Tesis doctoral |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Lenguaje: | Inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/39773 |
| Acceso en línea: | https://hdl.handle.net/10171/39773 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud |
| _version_ | 1878742331517042688 |
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| author | Mena-Varas, M. (María)|||/items/32f06fee-5408-4b4a-94b2-2827975f048a |
| author_browse | Mena-Varas, M. (María)|||/items/32f06fee-5408-4b4a-94b2-2827975f048a |
| author_facet | Mena-Varas, M. (María)|||/items/32f06fee-5408-4b4a-94b2-2827975f048a |
| author_role | author |
| collection | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| description | NKX2 homeobox family proteins play a role in cancer development. Molecular cloning of a translocation t(10;14)(q24;q32) from a marginal-zone B-cell lymphoma revealed NKX2-3 as an IGH partner gene, leading to increased NKX2-3 expression with respect to B lymphocytes. NKX2-3 overexpression was also detected in tumor cells from a subset of patients with extranodal and splenic marginal-zone lymphomas, but not with other mature B-cell malignancies. While Nkx2-3 deficient mice exhibited atrophic spleens with absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells showed progressive splenomegaly with marginal-zone expansion, and eventually developed tumors faithfully recapitulating the phenotype, cellular and molecular biology of human marginal-zone lymphomas. Mechanistically, NKX2-3 induced constitutive B-cell receptor (BCR) signaling by phosphorylating Lyn and Syk kinases. These molecules enhanced proliferation and eventually acquiring genomic rearrangements that triggered NF-κB and PI3K-AKT pathways to drive malignant transformation. This study implicates oncogenic NKX2-3 in marginal-zone lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human lymphoma. |
| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
| id | ES_f409e008ebb14e4db9bacff0e4bded5b |
| institution | Universidad de Navarra |
| instname_str | Universidad de Navarra |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:dadun.unav.edu:10171/39773 |
| publishDate | 2015 |
| publishDateSort | 2015 |
| reponame_str | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| spelling | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model Mena-Varas, M. (María)|||/items/32f06fee-5408-4b4a-94b2-2827975f048a Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud NKX2 homeobox family proteins play a role in cancer development. Molecular cloning of a translocation t(10;14)(q24;q32) from a marginal-zone B-cell lymphoma revealed NKX2-3 as an IGH partner gene, leading to increased NKX2-3 expression with respect to B lymphocytes. NKX2-3 overexpression was also detected in tumor cells from a subset of patients with extranodal and splenic marginal-zone lymphomas, but not with other mature B-cell malignancies. While Nkx2-3 deficient mice exhibited atrophic spleens with absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells showed progressive splenomegaly with marginal-zone expansion, and eventually developed tumors faithfully recapitulating the phenotype, cellular and molecular biology of human marginal-zone lymphomas. Mechanistically, NKX2-3 induced constitutive B-cell receptor (BCR) signaling by phosphorylating Lyn and Syk kinases. These molecules enhanced proliferation and eventually acquiring genomic rearrangements that triggered NF-κB and PI3K-AKT pathways to drive malignant transformation. This study implicates oncogenic NKX2-3 in marginal-zone lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human lymphoma. https://hdl.handle.net/10171/39773 |
| spellingShingle | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model Mena-Varas, M. (María)|||/items/32f06fee-5408-4b4a-94b2-2827975f048a Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud |
| title | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_full | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_fullStr | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_full_unstemmed | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_short | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_sort | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| topic | Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud |
| topic_facet | Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud |
| url | https://hdl.handle.net/10171/39773 |