Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model
Abstract Chronic lymphocytic leukemia (CLL) is a heterogeneous B cell malignancy characterized by the accumulation of functionally incompetent B lymphocytes. Despite the availability of highly effective treatments, CLL remains incurable, and the factors contributing to disease progression are not fu...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-86876-1 |
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| author | Lisa Pfeuffer Viola Siegert Riccardo Trozzo Katja Steiger Roland Rad Jürgen Ruland Maike Buchner |
| author_facet | Lisa Pfeuffer Viola Siegert Riccardo Trozzo Katja Steiger Roland Rad Jürgen Ruland Maike Buchner |
| author_sort | Lisa Pfeuffer |
| collection | DOAJ |
| description | Abstract Chronic lymphocytic leukemia (CLL) is a heterogeneous B cell malignancy characterized by the accumulation of functionally incompetent B lymphocytes. Despite the availability of highly effective treatments, CLL remains incurable, and the factors contributing to disease progression are not fully understood. Autoimmune complications frequently arise in CLL patients and are associated with poor clinical prognosis. This study investigates the connection between plasma cell-mediated autoimmunity and CLL progression using a mouse model that expresses an active Receptor Activator of NF-κB (RANK) in B cells (RK mice), where autoimmune manifestations coexist with CLL. Transcriptional profiling of RANK-driven leukemic cells revealed a more indolent form of CLL compared to the classical TCL1 model. The discovery of near-identical CDR3 regions in both plasma and CLL cells of RK mice suggests a shared progenitor and antigen driving both conditions. Deletion of Blimp-1, which prevents plasma cell differentiation, initially enhanced B1/CLL formation in young mice but nearly halted CLL progression, highlighting the significant influence of autoimmune complications on disease outcomes. This research underscores the intertwined nature of autoimmunity and CLL, suggesting that targeting inflammatory pathways could offer therapeutic potential for managing both conditions. |
| format | Article |
| id | doaj-art-4054855a24ba48a1a5493f238070f1a0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4054855a24ba48a1a5493f238070f1a02025-02-09T12:28:06ZengNature PortfolioScientific Reports2045-23222025-02-0115111310.1038/s41598-025-86876-1Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease modelLisa Pfeuffer0Viola Siegert1Riccardo Trozzo2Katja Steiger3Roland Rad4Jürgen Ruland5Maike Buchner6Institute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, TUM School of Medicine and HealthInstitute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, TUM School of Medicine and HealthTranslaTUM, Center for Translational Cancer Research, Technical University of MunichInstitute of Pathology, Technical University of MunichTranslaTUM, Center for Translational Cancer Research, Technical University of MunichInstitute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, TUM School of Medicine and HealthInstitute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, TUM School of Medicine and HealthAbstract Chronic lymphocytic leukemia (CLL) is a heterogeneous B cell malignancy characterized by the accumulation of functionally incompetent B lymphocytes. Despite the availability of highly effective treatments, CLL remains incurable, and the factors contributing to disease progression are not fully understood. Autoimmune complications frequently arise in CLL patients and are associated with poor clinical prognosis. This study investigates the connection between plasma cell-mediated autoimmunity and CLL progression using a mouse model that expresses an active Receptor Activator of NF-κB (RANK) in B cells (RK mice), where autoimmune manifestations coexist with CLL. Transcriptional profiling of RANK-driven leukemic cells revealed a more indolent form of CLL compared to the classical TCL1 model. The discovery of near-identical CDR3 regions in both plasma and CLL cells of RK mice suggests a shared progenitor and antigen driving both conditions. Deletion of Blimp-1, which prevents plasma cell differentiation, initially enhanced B1/CLL formation in young mice but nearly halted CLL progression, highlighting the significant influence of autoimmune complications on disease outcomes. This research underscores the intertwined nature of autoimmunity and CLL, suggesting that targeting inflammatory pathways could offer therapeutic potential for managing both conditions.https://doi.org/10.1038/s41598-025-86876-1 |
| spellingShingle | Lisa Pfeuffer Viola Siegert Riccardo Trozzo Katja Steiger Roland Rad Jürgen Ruland Maike Buchner Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model Scientific Reports |
| title | Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model |
| title_full | Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model |
| title_fullStr | Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model |
| title_full_unstemmed | Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model |
| title_short | Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model |
| title_sort | autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model |
| url | https://doi.org/10.1038/s41598-025-86876-1 |
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