دورية أكاديمية
The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy
| العنوان: | The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy |
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| المؤلفون: | Graham Packham, Serge Krysov, Alex Allen, Natalia Savelyeva, Andrew J. Steele, Francesco Forconi, Freda K. Stevenson |
| المصدر: | Haematologica, Vol 99, Iss 7 (2014) |
| بيانات النشر: | Ferrata Storti Foundation, 2014. |
| سنة النشر: | 2014 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Biologists and clinicians agree that the B-cell receptor influences the behavior of chronic lymphocytic leukemia, and promising new drugs are aimed at receptor-associated kinases. Engagement of surface immunoglobulin by antigen is a key driver of malignant cells with outcome influenced by the nature of the cell, the level of stimulation and the microenvironment. Analysis of surface immunoglobulin-mediated signaling in the two major disease subsets defined by IGHV mutational status reveals bifurcation of responses toward proliferation or anergy. Mutated chronic lymphocytic leukemia, generally of relatively good prognosis, is mainly, but not exclusively, driven towards anergy in vivo. In contrast, unmutated chronic lymphocytic leukemia shows less evidence for anergy in vivo retaining more responsiveness to surface immunoglobulin M-mediated signaling, possibly explaining increased tumor progression. Expression and function of surface immunoglobulin M in unmutated chronic lymphocytic leukemia appear rather homogeneous, but mutated chronic lymphocytic leukemia exhibits a highly heterogeneous profile that may relate to further variable clinical behavior within this subset. Anergy should increase susceptibility to apoptosis but, in leukemic cells, this may be countered by overexpression of the B-cell lymphoma-2 survival protein. Maintained anergy spreads to chemokines and adhesion molecules, restraining homing and migration. However, anergy is not necessarily completely benign, being able to reverse and regenerate surface immunoglobulin M-mediated responses. A two-pronged attack on proliferative and anti-apoptotic pathways may succeed. Increased understanding of how chronic lymphocytic leukemia cells are driven to anergy or proliferation should reveal predictive biomarkers of progression and of likely response to kinase inhibitors, which could assist therapeutic decisions. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| العلاقة: | https://haematologica.org/article/view/7077Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test |
| DOI: | 10.3324/haematol.2013.098384 |
| الوصول الحر: | https://doaj.org/article/d2a7a9b089924c67bdd942427907afc2Test |
| رقم الانضمام: | edsdoj.2a7a9b089924c67bdd942427907afc2 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2013.098384 |