Molecular characterization of the microenvironment in CLL-like monoclonal B cell lymphocytosis and early-stage chronic lymphocytic leukemia
The analysis of the microenvironment in CLL-like monoclonal B cell lymphocytosis (MBL) and early-stage chronic lymphocytic leukemia (CLL) is relevant for understanding the natural history of CLL. To this end, a total of 58 MBL, 54 early-stage CLL and 31 healthy subjects were extensively characterize...
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| Format: | doctoral thesis |
| Status: | Published version |
| Publication Date: | 2017 |
| Country: | España |
| Institution: | CBUC, CESCA |
| Repository: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/664506 |
| Online Access: | http://hdl.handle.net/10803/664506 |
| Access Level: | Open access |
| Keyword: | Chronic lymphocytic leukemia (CLLl) CLL-like monoclonal B cell lymphocytosis (MBL) Tumor microenvironment (TME) Inflammatory response Leucemia linfàtica crónica (LLC) Linfocitosis B monoclonal (LBM) de tipo LLC Microambiente tumoral Respuesta inflamatoria 577 |
| Summary: | The analysis of the microenvironment in CLL-like monoclonal B cell lymphocytosis (MBL) and early-stage chronic lymphocytic leukemia (CLL) is relevant for understanding the natural history of CLL. To this end, a total of 58 MBL, 54 early-stage CLL and 31 healthy subjects were extensively characterized by various immunological and molecular methods. Purified CD4+ and CD8+ mononuclear cells from peripheral blood were subjected to gene expression studies and T cell receptor (TR) repertoire analysis, whereas cytokine immunoassays were performed in serum samples. Gene expression studies in CD4+ cells revealed increased cytotoxic and inflammatory pathways, which were higher in MBL than in early-stage CLL. Gene dysregulation was not remarkable in CD8+ cells. Increased serum levels of cytokines such as IL8, IFNγ and TNFα were also observed in MBL, while early-stage CLL generally displayed lower cytokine levels, especially amongst cases bearing somatically hypermutated IGHV genes. TR analysis demonstrated oligoclonality in both entities with persisting T cell clones over time and increasing clonality within CD4+ T cells concurrently with the expansion of neoplastic B cells. Besides, identical T cell clonotypes were identified in different MBL/CLL cases. All these findings implicate inflammatory processes and antigenic elements in the immune background of CLL, whose effects are significantly altered during progression from MBL to CLL. |
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