In:
Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-10-02)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-017-00830-y
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2553671-0