The inhibitory receptor Siglec‐G controls the severity of chronic lymphocytic leukemia

Abstract Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults in the Western world. B cell receptor (BCR) signaling is known to be crucial for the pathogenesis and maintenance of CLL cells which develop from mature CD5 + B cells. BCR signaling is regulated by the inhibitory co‐receptor Siglec‐G and Siglec‐G‐deficient mice have an enlarged CD5 + B1a cell population. Here, we determine how Siglec‐G expression influences the severity of CLL. Our results show that Siglec‐G deficiency leads to earlier onset and more severe course of the CLL‐like disease in the murine Eμ‐TCL1 model. In contrast, mice overexpressing Siglec‐G on the B cell surface are almost completely protected from developing CLL‐like disease. Furthermore, we observe a downmodulation of the human ortholog Siglec‐10 from the surface of human CLL cells. These results demonstrate a critical role for Siglec‐G in disease progression in mice, and suggest that a similar mechanism for Siglec‐10 in human CLL may exist.