The importance of B cell receptor isotypes and stereotypes in chronic lymphocytic leukemia
| Autor: | Elisa Ten Hacken, Paolo Ghia, Maria Gounari, Jan A. Burger |
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| Přispěvatelé: | ten Hacken, E., Gounari, M., Ghia, P., Burger, J. A. |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Chronic lymphocytic leukemia B-cell receptor Receptors Antigen B-Cell Biology Immunoglobulin D Article 03 medical and health sciences 0302 clinical medicine immune system diseases hemic and lymphatic diseases medicine Humans B cell breakpoint cluster region Hematology medicine.disease Leukemia Lymphocytic Chronic B-Cell Isotype Immunoglobulin Isotype Immunoglobulin Isotypes 030104 developmental biology medicine.anatomical_structure Oncology Immunoglobulin M 030220 oncology & carcinogenesis Immunology biology.protein Tyrosine kinase Human Signal Transduction |
| Zdroj: | Leukemia. 33:287-298 |
| ISSN: | 1476-5551 0887-6924 |
| Popis: | B cell receptor (BCR) signaling is a central pathway promoting the survival and proliferation of normal and malignant B cells. Chronic lymphocytic leukemia (CLL) arises from mature B cells, expressing functional BCRs, mainly of immunoglobulin M (IgM) and IgD isotypes. Importantly, 30% of CLL patients express quasi-identical BCRs, the so-called “stereotyped” receptors, indicating the existence of common antigenic determinants, which may drive disease initiation and favor its progression. Although the antigenic specificity of IgM and IgD receptors is identical, there are distinct isotype-specific responses after IgM and IgD triggering. Here, we discuss the most important steps of normal B cell development, and highlight the importance of BCR signaling for CLL pathogenesis, with a focus on differences between IgM and IgD isotype signaling. We also highlight the main characteristics of CLL patient subsets, based on BCR stereotypy, and describe subset-specific BCR function and antigen-binding characteristics. Finally, we outline the key biologic and clinical responses to kinase inhibitor therapy, targeting the BCR-associated Bruton’s tyrosine kinase, phosphoinositide-3-kinase, and spleen tyrosine kinase in patients with CLL. |
| Databáze: | OpenAIRE |
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