The inhibitory receptor Siglec-G controls the severity of chronic lymphocytic leukemia
© 2023 The Authors. Published under the terms of the CC BY 4.0 license..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
EMBO reports - 24(2023), 8 vom: 03. Aug., Seite e56420 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Röder, Bettina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.08.2023 Date Revised 05.08.2023 published: Print-Electronic GEO: GSE227678 Citation Status MEDLINE |
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| doi: |
10.15252/embr.202256420 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359254454 |
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| 245 | 1 | 4 | |a The inhibitory receptor Siglec-G controls the severity of chronic lymphocytic leukemia |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a GEO: GSE227678 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BCR signaling | |
| 650 | 4 | |a CLL | |
| 650 | 4 | |a Siglec-10 | |
| 650 | 4 | |a Siglec-G overexpressing mice | |
| 650 | 4 | |a Siglecs | |
| 650 | 7 | |a Sialic Acid Binding Immunoglobulin-like Lectins |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
| 700 | 1 | |a Fahnenstiel, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Schäfer, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Budeus, Bettina |e verfasserin |4 aut | |
| 700 | 1 | |a Dampmann, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Eichhorn, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Angermüller, Sieglinde |e verfasserin |4 aut | |
| 700 | 1 | |a Brost, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Winkler, Thomas H |e verfasserin |4 aut | |
| 700 | 1 | |a Seifert, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Nitschke, Lars |e verfasserin |4 aut | |
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