Autonomous B-cell Receptor Signaling in Chronic Lymphocytic Leukemia

: Chronic lymphocytic leukemia (CLL) is driven by both antigen-dependent and antigen-independent cell-autonomous B-cell receptor (BcR) signaling. The latter has been documented in CLL cases in different disease subgroups and correlates with disease progression. Autonomous signaling is also relevant in monoclonal B-cell lymphocytosis and other B-cell malignancies, including diffuse large B-cell lymphoma and splenic marginal zone lymphoma. This article examines its molecular basis, prognostic significance, and potential therapeutic relevance, highlighting the need for novel strategies to overcome resistance and improve outcomes.