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

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Item Type:	Article
Title:	Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
Creators Name:	Mansouri, L., Noerenberg, D., Young, E., Mylonas, E., Abdulla, M., Frick, M., Asmar, F., Ljungstroem, V., Schneider, M., Yoshida, K., Skaftason, A., Pandzic, T., Gonzalez, B., Tasidou, A., Waldhueter, N., Rivas-Delgado, A., Angelopoulou, M., Ziepert, M., Arends, C.M., Couronne, L., Lenze, D., Baldus, C.D., Bastard, C., Okosun, J., Fitzgibbon, J., Doerken, B., Drexler, H.G., Roos-Weil, D., Schmitt, C.A., Munch-Petersen, H.D., Zenz, T., Hansmann, M.L., Strefford, J.C., Enblad, G., Bernard, O.A., Ralfkiaer, E., Erlanson, M., Korkolopoulou, P., Hultdin, M., Papadaki, T., Gronbaek, K., Lopez-Guillermo, A., Ogawa, S., Kueppers, R., Stamatopoulos, K., Stavroyianni, N., Kanellis, G., Rosenwald, A., Campo, E., Amini, R.M., Ott, G., Vassilakopoulos, T.P., Hummel, M., 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
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	128
Number:	23
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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