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Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma

Item Type:Article
Title:Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
Creators Name:Mansouri, L. and Noerenberg, D. and Young, E. and Mylonas, E. and Abdulla, M. and Frick, M. and Asmar, F. and Ljungstroem, V. and Schneider, M. and Yoshida, K. and Skaftason, A. and Pandzic, T. and Gonzalez, B. and Tasidou, A. and Waldhueter, N. and Rivas-Delgado, A. and Angelopoulou, M. and Ziepert, M. and Arends, C.M. and Couronne, L. and Lenze, D. and Baldus, C.D. and Bastard, C. and Okosun, J. and Fitzgibbon, J. and Doerken, B. and Drexler, H.G. and Roos-Weil, D. and Schmitt, C.A. and Munch-Petersen, H.D. and Zenz, T. and Hansmann, M.L. and Strefford, J.C. and Enblad, G. and Bernard, O.A. and Ralfkiaer, E. and Erlanson, M. and Korkolopoulou, P. and Hultdin, M. and Papadaki, T. and Gronbaek, K. and Lopez-Guillermo, A. and Ogawa, S. and Kueppers, R. and Stamatopoulos, K. and Stavroyianni, N. and Kanellis, G. and Rosenwald, A. and Campo, E. and Amini, R.M. and Ott, G. and Vassilakopoulos, T.P. and Hummel, M. and Rosenquist, R. and Damm, F.
Abstract:We recently reported a truncating deletion in the NFKBIE gene, which encodes IkappaB, a negative feedback regulator of NF-kappaB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal-zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary CNS lymphoma (3-4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases, 22.7%) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases, 27.3%). NFKBIE-deleted PMBL patients were more often therapy-refractory (P=.022) and displayed inferior outcome compared to wildtype patients (5-year survival: 59% vs. 78%; P=.034); however they appeared to benefit from radiotherapy (P=.022) and rituximab-containing regimens (P=.074). NFKBIE aberrations remained an independent factor in multivariate analysis (P=.003), also when restricting to immunochemotherapy-treated patients (P=.008). Whole-exome sequencing and gene expression-profiling verified the importance of NF-kappaB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.
Keywords:Lymphoma, PMBL, NFKBIE, Mutation, Prognosis
Publisher:American Society of Hematology
Page Range:2666-2670
Date:15 December 2016
Official Publication:https://doi.org/10.1182/blood-2016-03-704528
PubMed:View item in PubMed

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