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

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 E & mu;-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.

Automated summary

Loss of Siglec-G leads to increased severity and earlier onset of CLL in mice, while overexpression of Siglec-G on B cells protects against CLL development. Furthermore, downregulation of the human ortholog Siglec-10 is observed on the surface of human CLL cells. These findings highlight the critical role of Siglec-G in disease progression and suggest a potential similar mechanism for Siglec-10 in human CLL.