The NF-κB pathway is rarely spontaneously activated in mantle cell lymphoma (MCL) cell lines and patient's samples

Abstract

In this study, we investigated the role of NF-κB (canonical and alternative pathways) in the survival or proliferation of mantle cell lymphoma (MCL) cell lines. P50/p65 complexes were detectable by EMSA assays in 4/5 cell lines. Stable expression of a dominant-negative form of IkBa had no effect on proliferation nor on apoptosis in EBV-negative cell lines. Three out of 4 of the cell lines tested exhibited Phospho-p65 (Ser(536)). The alternative NF-κB pathway was not activated in 4/5 cell lines tested. Patient samples were also studied by Western blot, EMSA and Immunohistochemistry (IHC). No p50/p65 complexes were detected in cells freshly collected from 7 patients, but 1/7 cells exhibited Phospho-p65 (Ser(536)). We investigated immunohistochemically, the expression of NF-κB in 86 patients enrolled in two multicentre prospective trials. Patients with MCL exhibiting negative or positive cytoplasmic expression of NF-κB had a median overall survival of 35.7months compared to 22.4months for patients with nuclear NF-κB expression (p=0.0193). All these data suggest that NF-κB does not play a key role in proliferation and apoptotic processes in MCL cell lines. In patient samples, the presence of p65 in the nucleus reflecting NF-κB activation is rare but associated with a poor outcome.

Keywords: Biomarker; Mantle cell lymphoma; NF-κB; Prognosis.