Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.

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Bucher P, Erdmann T, Grondona P, Xu W, Schmitt A, Schürch C, Zapukhlyak M, Schönfeld C, Serfling E, Kramer D, Grau M, Klener P, Lengerke C, Schulze-Osthoff K, Lenz G, Hailfinger S