biostudies-literatureUnknown15(1)Pfeuffer LChronic 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. ThScientific reports4117https://www.ebi.ac.uk/biostudies/studies/S-EPMC11791097biostudies-literatureAutoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model.PMC11791097Trozzo RRad RRuland JBuchner MPfeuffer LSiegert VSteiger KfalseAutoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model.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. Th2025-01-01T00:00:00Z2025 Feb2025-04-19T16:21:15.353Z2025-04-19T16:21:15.353ZS-EPMC117910973990093710.1038/s41598-025-86876-1