Role of ZEB factors in B cell activation and malignant progression
[eng] ZEB1 and ZEB2 are two transcription factors best known for their role driving a dedifferentiation process, commonly referred as epithelial to mesenchymal transition (EMT). This process is carried out either in multiple physiological and pathological conditions, such as normal development and t...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/186256 |
| Acceso en línea: | https://hdl.handle.net/2445/186256 http://hdl.handle.net/10803/674399 |
| Access Level: | acceso abierto |
| Palabra clave: | Factors de transcripció Limfomes Cèl·lules B Transcription factors Lymphomas B cells |
| Sumario: | [eng] ZEB1 and ZEB2 are two transcription factors best known for their role driving a dedifferentiation process, commonly referred as epithelial to mesenchymal transition (EMT). This process is carried out either in multiple physiological and pathological conditions, such as normal development and tumor progression. More recently their role in T cell development and T cell leukemias have been studied but their role in B-cell activation and B cell malignant progression remains still poorly understood. In this PhD dissertation, it was found that both ZEB1 and ZEB2 factors are expressed during the differentiation of the B cell lineage and specifically in the Germinal Center (GC) B cells. ZEB1 is required for GC formation and to prepare a correct T-dependent response in front of a specific antigen. Due to different chromosomal alterations and mutations, the GC B cells can undergo malignant transformation and give rise to different subtypes of B cell lymphoma, being diffuse large B cell lymphoma (DLBCL) the most common. It was found that ZEB1 and ZEB2 are involved in the progression of DLBCL as they regulate the DLBCL proliferation and cell metabolism, being ZEB1 a marker of poorer prognosis and associated to higher proliferation rate of tumoral cells and ZEB2 having an inversed pattern. These reversed expression patterns of ZEB1 and ZEB2 was also found in multiple myeloma (MM), where ZEB2 acts as an anti-tumoral marker and is associated with a pre-malignant stage, the monoclonal gammopathy of undetermined significance (MGUS). ZEB1 acts as a pro-tumoral gene, associated with the malignization of the disease and is associated with different hallmarks: poorer treatment response, cell migration, and in the bone formation. The results set ZEB1 and ZEB2 as potent prognosis markers in lymphomas and highlight that their potential as therapeutic targets needs to be assessed in the future. |
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