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Skaftason, Aron
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Mansouri, L., Noerenberg, D., Young, E., Mylonas, E., Abdulla, M., Frick, M., . . . Damm, F. (2016). Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma. Blood, 128(23), 2666-2670
Open this publication in new window or tab >>Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
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2016 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 128, no 23, p. 2666-2670Article in journal (Refereed) Published
Abstract [en]

We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBϵ, a negative feedback regulator of NF-κB, 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). NFKBIEaberrations 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-κB 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.

National Category
Hematology Clinical Laboratory Medicine
Research subject
Molecular Genetics; Pathology
urn:nbn:se:uu:diva-314939 (URN)10.1182/blood-201603-704528 (DOI)000392652300015 ()27670424 (PubMedID)
German Research Foundation (DFG), DA1787/1-1Swedish Cancer SocietySwedish Research Council

L.M., D.N., and E.Y. contributed equally to this study as joint first authors.

R.R. and F.D. contributed equally as joint senior authors.

Available from: 2017-02-07 Created: 2017-02-07 Last updated: 2019-03-29Bibliographically approved

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