NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia
| Autor: | Andreas Kirschniak, Anjana Rao, Michael Gutknecht, Felicia M. Truckenmüller, Hans-Georg Kopp, Jonas S. Heitmann, Stefanie Bugl, Ursula Kohlhofer, Alexander R. Fuchs, Juliane Lazarus, Lothar Kanz, Michael Haap, Stefan Wirths, Melanie Märklin, Sebastian Jonas Saur, Leticia Quintanilla-Martinez, Martin Müller, Hans-Georg Rammensee, Helmut R. Salih |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science Ubiquitin-Protein Ligases B-cell receptor Regulator General Physics and Astronomy Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice immune system diseases hemic and lymphatic diseases medicine Animals Humans Proto-Oncogene Proteins c-cbl B-cell lymphoma lcsh:Science Gene Transcription factor neoplasms Early Growth Response Protein 2 Adaptor Proteins Signal Transducing Clonal Anergy Multidisciplinary Lymphocytic leukaemia NFATC Transcription Factors General Chemistry medicine.disease Phenotype Leukemia Lymphocytic Chronic B-Cell Gene Expression Regulation Neoplastic 030104 developmental biology Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Immunology lcsh:Q Signal transduction |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-017-00830-y |
| Popis: | Chronic lymphocytic leukaemia (CLL) is a clonal disorder of mature B cells. Most patients are characterised by an indolent disease course and an anergic phenotype of their leukaemia cells, which refers to a state of unresponsiveness to B cell receptor stimulation. Up to 10% of CLL patients transform from an indolent subtype to an aggressive form of B cell lymphoma over time (Richter´s syndrome) and show a significantly worse treatment outcome. Here we show that B cell-specific ablation of Nfat2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependent genes including Cbl-b, Grail, Egr2 and Lck. In summary, this study identifies NFAT2 as a crucial regulator of the anergic phenotype in CLL. NFAT2 is a transcription factor that has been linked with chronic lymphocytic leukaemia (CLL), but its functions in CLL manifestation are still unclear. Here the authors show, by analysing mouse CLL models and characterising biopsies from CLL patients, that NFAT2 is an important regulator for the anergic phenotype of CLL. |
| Databáze: | OpenAIRE |
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