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Nat Commun. 2017 Oct 2;8(1):755. doi: 10.1038/s41467-017-00830-y.

NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia.

Author information

1
Department of Oncology, Haematology and Immunology, University of Tübingen, Tübingen, 72076, Germany.
2
Department of Pathology, University of Tübingen, Tübingen, 72076, Germany.
3
Department of Immunology, University of Tübingen, Tübingen, 72076, Germany.
4
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.
5
Department of Endocrinology, Diabetology, Clinical Pathology and Metabolism, University of Tübingen, Tübingen, 72076, Germany.
6
Department of Surgery, University of Tübingen, Tübingen, 72076, Germany.
7
La Jolla Institute of Allergy and Immunology, La Jolla, CA, 92037, USA.
8
Department of Oncology, Haematology and Immunology, University of Tübingen, Tübingen, 72076, Germany. martin.mueller@med.uni-tuebingen.de.

Abstract

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.

PMID:
28970470
PMCID:
PMC5624906
DOI:
10.1038/s41467-017-00830-y
[Indexed for MEDLINE]
Free PMC Article

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