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

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Listed:
  • Melanie Märklin

    (University of Tübingen)

  • Jonas S. Heitmann

    (University of Tübingen)

  • Alexander R. Fuchs

    (University of Tübingen)

  • Felicia M. Truckenmüller

    (University of Tübingen)

  • Michael Gutknecht

    (University of Tübingen)

  • Stefanie Bugl

    (University of Tübingen)

  • Sebastian J. Saur

    (University of Tübingen)

  • Juliane Lazarus

    (University of Tübingen)

  • Ursula Kohlhofer

    (University of Tübingen)

  • Leticia Quintanilla-Martinez

    (University of Tübingen)

  • Hans-Georg Rammensee

    (University of Tübingen)

  • Helmut R. Salih

    (University of Tübingen
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ))

  • Hans-Georg Kopp

    (University of Tübingen)

  • Michael Haap

    (University of Tübingen)

  • Andreas Kirschniak

    (University of Tübingen)

  • Lothar Kanz

    (University of Tübingen)

  • Anjana Rao

    (La Jolla Institute of Allergy and Immunology)

  • Stefan Wirths

    (University of Tübingen)

  • Martin R. Müller

    (University of Tübingen)

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.

Suggested Citation

  • Melanie Märklin & Jonas S. Heitmann & Alexander R. Fuchs & Felicia M. Truckenmüller & Michael Gutknecht & Stefanie Bugl & Sebastian J. Saur & Juliane Lazarus & Ursula Kohlhofer & Leticia Quintanilla-M, 2017. "NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00830-y
    DOI: 10.1038/s41467-017-00830-y
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