Περίληψη:
We recently reported a truncating deletion in the NFKBIE gene, which encodes IκB, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n 5 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 central nervous system lymphoma (3% to 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 5 .022) and displayed inferior outcome compared with wild-Type patients (5-year survival, 59% vs 78%; P 5 .034); however, they appeared to benefit from radiotherapy (P 5 .022) and rituximab-containing regimens (P 5 .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P 5 .003) and when restricting the analysis to immunochemotherapy-Treated patients (P 5 .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. © 2016 by The American Society of Hematology.
Συγγραφείς:
Mansouri, L.
Noerenberg, D.
Young, E.
Mylonas, E.
Abdulla, M.
Frick, M.
Asmar, F.
Ljungström, 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.
Couronné, L.
Lenze, D.
Baldus, C.D.
Bastard, C.
Okosun, J.
Fitzgibbon, J.
Dörken, 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.
Grønbæk, K.
Lopez-Guillermo, A.
Ogawa, S.
Küppers, R.
Stamatopoulos, K.
Stavroyianni, N.
Kanellis, G.
Rosenwald, A.
Campo, E.
Amini, R.-M.
Ott, G.
Vassilakopoulos, T.P.
Hummel, M.
Rosenquist, R.
Damm, F.
Λέξεις-κλειδιά:
bleomycin; cyclophosphamide; doxorubicin; immunoglobulin enhancer binding protein; prednisolone; prednisone; rituximab; vincristine; vindesine; I kappa B; NFKBIE protein, human; oncoprotein; tumor marker, acute lymphoblastic leukemia; adult; aged; Article; B cell lymphoma; cancer immunotherapy; cancer patient; cancer prognosis; cancer radiotherapy; cancer survival; classical Hodgkin lymphoma; clinical outcome; comparative study; controlled study; diffuse large B cell lymphoma; female; follicular lymphoma; follow up; gene; gene deletion; gene expression profiling; gene frequency; genetic association; Hodgkin disease; human; major clinical study; male; mantle cell lymphoma; mediastinum cancer; mutational analysis; NFKBIE gene; nucleotide sequence; primary central nervous system lymphoma; primary tumor; priority journal; regulatory mechanism; splenic marginal zone lymphoma; T cell leukemia; treatment response; whole exome sequencing; adolescent; B cell lymphoma; clinical trial; disease free survival; genetics; mediastinum tumor; middle aged; mortality; multicenter study; survival rate, Adolescent; Adult; Aged; Biomarkers, Tumor; Disease-Free Survival; Female; Gene Deletion; Humans; I-kappa B Proteins; Lymphoma, B-Cell; Male; Mediastinal Neoplasms; Middle Aged; Proto-Oncogene Proteins; Survival Rate
