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

Language
en
Document Type
Article
Issue Date
2023-07-10
Issue Date
2023-08-03
Authors
Röder, Bettina
Fahnenstiel, Hannah
Schäfer, Simon
Budeus, Bettina
Dampmann, Maria
Eichhorn, Melanie
Angermüller, Sieglinde
Brost, Claudia
Winkler, Thomas H
Seifert, Marc
Editor
Publisher
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.

Abstract
Synopsis

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Deficiency of the inhibitory receptor Siglec‐G in mice leads to earlier onset and more severe chronic lymphocytic leukemia (CLL). In contrast, overexpression of Siglec‐G on B cells protects mice from CLL.

Deficiency of Siglec‐G in a mouse model leads to more severe chronic lymphocytic leukemia.

Mice overexpressing Siglec‐G on the B cell surface are protected from CLL disease.

Siglec‐10, the human ortholog to Siglec‐G, is down‐modulated on CLL cells of human patients.

Abstract

Deficiency of the inhibitory receptor Siglec‐G in mice leads to earlier onset and more severe chronic lymphocytic leukemia (CLL). In contrast, overexpression of Siglec‐G on B cells protects mice from CLL. image

Journal Title
EMBO reports
Volume
24
Issue
8
Citation
EMBO reports 24.8 (2023). DOI:10.15252/embr.202256420
URN
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