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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Märklin M,Heitmann JS,Fuchs AR,Truckenmüller FM,Gutknecht M,Bugl S,Saur SJ,Lazarus J,Kohlhofer U,Quintanilla-Martinez L,Rammensee HG,Salih HR,Kopp HG,Haap M,Kirschniak A,Kanz L,Rao A,Wirths S,Müller MR

doi

10.1038/s41467-017-00830-y

subject

Has Abstract

pub_date

2017-10-02 00:00:00

pages

755

issue

1

issn

2041-1723

pii

10.1038/s41467-017-00830-y

journal_volume

8

pub_type

杂志文章

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