title: 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.
authors.affiliation: Gustave Roussy Institut, Institut National de la Santé et de la Recherche Médicale (INSERM) unité (U) 1009, Université Paris Sud, Villejuif, France.
authors.forename: V
authors.initials: V
authors.lastname: Camara-Clayette
authors.affiliation: Imaging and Cytometry Platform, Gustave Roussy Institut, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Lecluse
authors.affiliation: Department of Internal Medicine and Hematology, University Hospitals of Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schrader
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Gustave Roussy Institut, Institut National de la Santé et de la Recherche Médicale (INSERM) unité (U) 1009, Université Paris Sud, Villejuif, France.
authors.forename: W
authors.initials: W
authors.lastname: Vainchenker
authors.affiliation: Centre National de la Recherche Scientifique (CNRS) UMR 8147, Hôpital Necker, Paris, France; Service d'Hématologie, Hôpital Necker, Assistance Publique des Hôpitaux de Paris, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Gustave Roussy Institut, Institut National de la Santé et de la Recherche Médicale (INSERM) unité (U) 1009, Université Paris Sud, Villejuif, France; Département de Médecine, Gustave Roussy Institut, Villejuif, France. Electronic address: ribrag@igr.fr.
authors.forename: V
authors.initials: V
authors.lastname: Ribrag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B
keywords: Biomarker; Mantle cell lymphoma; NF-κB; Prognosis