Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia
NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The...
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| Published in | The Journal of experimental medicine Vol. 212; no. 6; pp. 833 - 843 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
The Rockefeller University Press
01.06.2015
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| Subjects | |
| Online Access | Get full text |
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| Abstract | NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis. |
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| AbstractList | Mansouri et al. applied targeted deep sequencing to identify mutations within NF- Kappa B core complex genes in CLL. NFKBIE, the gene encoding the inhibitory I Kappa B epsilon molecule, was most frequently mutated, especially in poor-prognostic subgroups of CLL. The authors show that NFKBIE mutations were associated with significantly reduced IkB epsilon expression and p65 inhibition, ultimately leading to NF- Kappa B activation and a more aggressive disease. NF- Kappa B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF- Kappa B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I Kappa B epsilon , a negative regulator of NF- Kappa B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I Kappa B epsilon protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I Kappa B epsilon loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF- Kappa B deregulation during lymphomagenesis. NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis. Mansouri et al. applied targeted deep sequencing to identify mutations within NF-κB core complex genes in CLL. NFKBIE , the gene encoding the inhibitory IκBε molecule, was most frequently mutated, especially in poor-prognostic subgroups of CLL. The authors show that NFKBIE mutations were associated with significantly reduced IkBε expression and p65 inhibition, ultimately leading to NF-κB activation and a more aggressive disease. NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE -deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis. NF-kappa B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-kappa B pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes I kappa B epsilon, a negative regulator of NF-kappa B in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced I kappa B epsilon protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that I kappa B epsilon loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-kappa B deregulation during lymphomagenesis. |
| Author | Stamatopoulos, Kostas Mansouri, Larry Enblad, Gunilla Hellström, Mats Bhoi, Sujata Pospisilova, Sarka Arngården, Linda Gunnarsson, Rebeqa Rung, Johan Falk-Sörqvist, Elin Cortese, Diego Rosenquist, Richard Yan, Xiao-Jie Chiorazzi, Nicholas Muggen, Alice F Sutton, Lesley-Ann Davi, Frederic Söderberg, Ola Ljungström, Viktor Larsson, Jimmy Nilsson, Mats Sander, Birgitta Langerak, Anton W Strefford, Jonathan C Kalushkova, Antonia Jernberg-Wiklund, Helena Smedby, Karin E Lönn, Peter Bondza, Sina Young, Emma Plevova, Karla Ghia, Paolo Belessi, Chrysoula Juliusson, Gunnar |
| AuthorAffiliation | 5 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Stockholm, Sweden 6 Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden 10 Department of Hematology, Pitié-Salpêtrière Hospital, F-75013 Paris, France 8 Hematology Department, General Hospital of Nikea, 18454 Piraeus, Greece 3 Department of Immunology, Erasmus MC, University Medical Center Rotterdam, 3000 CE Rotterdam, Netherlands 1 Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden 7 Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, 22184 Lund, Sweden 2 Central European Institute of Technology, Masaryk University and University Hospital Brno, 601 77 Brno, Czech Republic 14 Institute of Applied Biosciences, Center for Research and Technology Hellas, 57001 Thessaloniki, Greece 4 The Karches Center for Chronic Lymphocytic |
| AuthorAffiliation_xml | – name: 4 The Karches Center for Chronic Lymphocytic Leukemia Research, The Feinstein Institute for Medical Research, Manhasset, NY 11030 – name: 6 Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden – name: 8 Hematology Department, General Hospital of Nikea, 18454 Piraeus, Greece – name: 5 Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet and Karolinska University Hospital, 141 86 Huddinge, Stockholm, Sweden – name: 11 Cordeliers Research Center, UMR_S 1138, UPMC University of Paris 6, F-75005 Paris, France – name: 7 Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, 22184 Lund, Sweden – name: 10 Department of Hematology, Pitié-Salpêtrière Hospital, F-75013 Paris, France – name: 15 Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, 106 91 Stockholm, Sweden – name: 12 Divisione di Oncologia Sperimentale, Dipartimento di Onco-Ematologia, IRCCS Istituto Scientifico San Raffaele and Fondazione Centro San Raffaele, 20132 Milano, Italy – name: 13 Università Vita-Salute San Raffaele, 20132 Milano, Italy – name: 3 Department of Immunology, Erasmus MC, University Medical Center Rotterdam, 3000 CE Rotterdam, Netherlands – name: 2 Central European Institute of Technology, Masaryk University and University Hospital Brno, 601 77 Brno, Czech Republic – name: 1 Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden – name: 9 Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, England, UK – name: 14 Institute of Applied Biosciences, Center for Research and Technology Hellas, 57001 Thessaloniki, Greece |
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Karolinska Institutet, 171 76 Stockholm, Sweden – sequence: 20 givenname: Gunnar surname: Juliusson fullname: Juliusson, Gunnar organization: Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, 22184 Lund, Sweden – sequence: 21 givenname: Chrysoula surname: Belessi fullname: Belessi, Chrysoula organization: Hematology Department, General Hospital of Nikea, 18454 Piraeus, Greece – sequence: 22 givenname: Johan surname: Rung fullname: Rung, Johan organization: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden – sequence: 23 givenname: Nicholas surname: Chiorazzi fullname: Chiorazzi, Nicholas organization: The Karches Center for Chronic Lymphocytic Leukemia Research, The Feinstein Institute for Medical Research, Manhasset, NY 11030 – sequence: 24 givenname: Jonathan C surname: Strefford fullname: Strefford, Jonathan C organization: Cancer Sciences Academic Unit, Faculty of Medicine, University 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Jernberg-Wiklund, Helena organization: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden – sequence: 30 givenname: Paolo surname: Ghia fullname: Ghia, Paolo organization: Divisione di Oncologia Sperimentale, Dipartimento di Onco-Ematologia, IRCCS Istituto Scientifico San Raffaele and Fondazione Centro San Raffaele, 20132 Milano, Italy Università Vita-Salute San Raffaele, 20132 Milano, Italy – sequence: 31 givenname: Ola surname: Söderberg fullname: Söderberg, Ola organization: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden – sequence: 32 givenname: Kostas surname: Stamatopoulos fullname: Stamatopoulos, Kostas organization: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden Institute of Applied Biosciences, Center for Research and Technology Hellas, 57001 Thessaloniki, Greece – sequence: 33 givenname: Mats surname: Nilsson fullname: Nilsson, Mats organization: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, 106 91 Stockholm, Sweden – sequence: 34 givenname: Richard surname: Rosenquist fullname: Rosenquist, Richard email: richard.rosenquist@igp.uu.se organization: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, 751 05 Uppsala, Sweden richard.rosenquist@igp.uu.se |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25987724$$D View this record in MEDLINE/PubMed https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-119056$$DView record from Swedish Publication Index https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-279237$$DView record from Swedish Publication Index https://lup.lub.lu.se/record/5448787$$DView record from Swedish Publication Index http://kipublications.ki.se/Default.aspx?queryparsed=id:131410081$$DView record from Swedish Publication Index |
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| Cites_doi | 10.1182/blood-2011-11-393694 10.1158/2159-8290.CD-14-0104 10.1016/j.semcancer.2013.04.002 10.1038/nmeth947 10.1182/blood-2007-06-093906 10.14806/ej.17.1.200 10.1038/nature08638 10.1084/jem.20080238 10.4161/onci.1.1.18400 10.1101/cshperspect.a000109 10.1038/leu.2014.196 10.1016/j.molimm.2008.03.002 10.1002/ijc.29169 10.1182/blood-2013-02-486209 10.1073/pnas.1311846111 10.1016/j.it.2004.03.008 10.1182/blood.V95.4.1420.004k12_1420_1426 10.1093/jnci/dji022 10.1093/nar/19.9.2499 10.1002/path.1454 10.1093/biostatistics/4.2.249 10.1182/blood-2006-03-012948 10.1084/jem.194.11.1625 10.1084/jem.194.11.1639 10.1182/blood-2010-05-284984 10.1038/nature07968 10.1093/nar/gkq603 10.1016/S2352-3026(14)00005-2 10.1038/leu.2013.98 10.1046/j.1365-3083.1999.00604.x 10.1038/ng.2900 10.4049/jimmunol.1302351 |
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| References | 26034117 - J Exp Med. 2015 Jun 1;212(6):830-1 Hömig-Hölzel (2023072603015268900_bib16) 2008; 205 Staudt (2023072603015268900_bib32) 2010; 2 Gunawardana (2023072603015268900_bib13) 2014; 46 Siemer (2023072603015268900_bib27) 2008; 45 Mathews Griner (2023072603015268900_bib20) 2014; 111 Baliakas (2023072603015268900_bib5) 2015; 29 Davis (2023072603015268900_bib10) 2010; 463 Damm (2023072603015268900_bib9) 2014; 4 Gao (2023072603015268900_bib12) 2015; 136 Andrews (2023072603015268900_bib3) 1991; 19 Martin (2023072603015268900_bib19) 2011; 17 Rosén (2023072603015268900_bib22) 1986; 5 Rossi (2023072603015268900_bib25) 2013; 23 Rosén (2023072603015268900_bib23) 2012; 1 Hallek (2023072603015268900_bib14) 2008; 111 Agathangelidis (2023072603015268900_bib1) 2012; 119 Alves (2023072603015268900_bib2) 2014; 192 Rosenwald (2023072603015268900_bib24) 2001; 194 Stamatopoulos (2023072603015268900_bib31) 2007; 109 Emmerich (2023072603015268900_bib11) 2003; 201 Rossi (2023072603015268900_bib26) 2013; 121 Wang (2023072603015268900_bib34) 2010; 38 Bonizzi (2023072603015268900_bib7) 2004; 25 Baliakas (2023072603015268900_bib4) 2014; 1 Strefford (2023072603015268900_bib33) 2013; 27 Smedby (2023072603015268900_bib28) 2005; 97 Herishanu (2023072603015268900_bib15) 2011; 117 Klein (2023072603015268900_bib18) 2001; 194 Söderberg (2023072603015268900_bib29) 1999; 50 Compagno (2023072603015268900_bib8) 2009; 459 Söderberg (2023072603015268900_bib30) 2006; 3 Irizarry (2023072603015268900_bib17) 2003; 4 Benjamini (2023072603015268900_bib6) 1995; 57 Nilsson (2023072603015268900_bib21) 2000; 95 |
| References_xml | – volume: 119 start-page: 4467 year: 2012 ident: 2023072603015268900_bib1 article-title: Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies publication-title: Blood. doi: 10.1182/blood-2011-11-393694 contributor: fullname: Agathangelidis – volume: 4 start-page: 1088 year: 2014 ident: 2023072603015268900_bib9 article-title: Acquired initiating mutations in early hematopoietic cells of CLL patients publication-title: Cancer Discov. doi: 10.1158/2159-8290.CD-14-0104 contributor: fullname: Damm – volume: 23 start-page: 422 year: 2013 ident: 2023072603015268900_bib25 article-title: Genetic aberrations of signaling pathways in lymphomagenesis: revelations from next generation sequencing studies publication-title: Semin. Cancer Biol. doi: 10.1016/j.semcancer.2013.04.002 contributor: fullname: Rossi – volume: 3 start-page: 995 year: 2006 ident: 2023072603015268900_bib30 article-title: Direct observation of individual endogenous protein complexes in situ by proximity ligation publication-title: Nat. Methods. doi: 10.1038/nmeth947 contributor: fullname: Söderberg – volume: 111 start-page: 5446 year: 2008 ident: 2023072603015268900_bib14 article-title: Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines publication-title: Blood. doi: 10.1182/blood-2007-06-093906 contributor: fullname: Hallek – volume: 17 start-page: 10 year: 2011 ident: 2023072603015268900_bib19 article-title: Cutadapt removes adapter sequences from high-throughput sequencing reads publication-title: EMBnet Journal. doi: 10.14806/ej.17.1.200 contributor: fullname: Martin – volume: 463 start-page: 88 year: 2010 ident: 2023072603015268900_bib10 article-title: Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma publication-title: Nature. doi: 10.1038/nature08638 contributor: fullname: Davis – volume: 205 start-page: 1317 year: 2008 ident: 2023072603015268900_bib16 article-title: Constitutive CD40 signaling in B cells selectively activates the noncanonical NF-κB pathway and promotes lymphomagenesis publication-title: J. Exp. Med. doi: 10.1084/jem.20080238 contributor: fullname: Hömig-Hölzel – volume: 1 start-page: 18 year: 2012 ident: 2023072603015268900_bib23 article-title: Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection publication-title: OncoImmunology. doi: 10.4161/onci.1.1.18400 contributor: fullname: Rosén – volume: 2 start-page: a000109 year: 2010 ident: 2023072603015268900_bib32 article-title: Oncogenic activation of NF-κB publication-title: Cold Spring Harb. Perspect. Biol. doi: 10.1101/cshperspect.a000109 contributor: fullname: Staudt – volume: 29 start-page: 329 year: 2015 ident: 2023072603015268900_bib5 article-title: Recurrent mutations refine prognosis in chronic lymphocytic leukemia publication-title: Leukemia. doi: 10.1038/leu.2014.196 contributor: fullname: Baliakas – volume: 45 start-page: 3133 year: 2008 ident: 2023072603015268900_bib27 article-title: EBV transformation overrides gene expression patterns of B cell differentiation stages publication-title: Mol. Immunol. doi: 10.1016/j.molimm.2008.03.002 contributor: fullname: Siemer – volume: 57 start-page: 289 year: 1995 ident: 2023072603015268900_bib6 article-title: Controlling the false discovery rate: a practical and powerful approach to multiple testing publication-title: J. R. Stat. Soc., B. contributor: fullname: Benjamini – volume: 136 start-page: E623 year: 2015 ident: 2023072603015268900_bib12 article-title: Genome-wide small nucleolar RNA expression analysis of lung cancer by next-generation deep sequencing publication-title: Int. J. Cancer. doi: 10.1002/ijc.29169 contributor: fullname: Gao – volume: 5 start-page: 185 year: 1986 ident: 2023072603015268900_bib22 article-title: A T-helper cell x Molt4 human hybridoma constitutively producing B-cell stimulatory and inhibitory factors publication-title: Lymphokine Res. contributor: fullname: Rosén – volume: 121 start-page: 4902 year: 2013 ident: 2023072603015268900_bib26 article-title: Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia publication-title: Blood. doi: 10.1182/blood-2013-02-486209 contributor: fullname: Rossi – volume: 111 start-page: 2349 year: 2014 ident: 2023072603015268900_bib20 article-title: High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells publication-title: Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.1311846111 contributor: fullname: Mathews Griner – volume: 25 start-page: 280 year: 2004 ident: 2023072603015268900_bib7 article-title: The two NF-κB activation pathways and their role in innate and adaptive immunity publication-title: Trends Immunol. doi: 10.1016/j.it.2004.03.008 contributor: fullname: Bonizzi – volume: 95 start-page: 1420 year: 2000 ident: 2023072603015268900_bib21 article-title: Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells publication-title: Blood. doi: 10.1182/blood.V95.4.1420.004k12_1420_1426 contributor: fullname: Nilsson – volume: 97 start-page: 199 year: 2005 ident: 2023072603015268900_bib28 article-title: Ultraviolet radiation exposure and risk of malignant lymphomas publication-title: J. Natl. Cancer Inst. doi: 10.1093/jnci/dji022 contributor: fullname: Smedby – volume: 19 start-page: 2499 year: 1991 ident: 2023072603015268900_bib3 article-title: A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells publication-title: Nucleic Acids Res. doi: 10.1093/nar/19.9.2499 contributor: fullname: Andrews – volume: 201 start-page: 413 year: 2003 ident: 2023072603015268900_bib11 article-title: Inactivating I kappa B epsilon mutations in Hodgkin/Reed–Sternberg cells publication-title: J. Pathol. doi: 10.1002/path.1454 contributor: fullname: Emmerich – volume: 4 start-page: 249 year: 2003 ident: 2023072603015268900_bib17 article-title: Exploration, normalization, and summaries of high density oligonucleotide array probe level data publication-title: Biostatistics. doi: 10.1093/biostatistics/4.2.249 contributor: fullname: Irizarry – volume: 109 start-page: 259 year: 2007 ident: 2023072603015268900_bib31 article-title: Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations publication-title: Blood. doi: 10.1182/blood-2006-03-012948 contributor: fullname: Stamatopoulos – volume: 194 start-page: 1625 year: 2001 ident: 2023072603015268900_bib18 article-title: Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells publication-title: J. Exp. Med. doi: 10.1084/jem.194.11.1625 contributor: fullname: Klein – volume: 194 start-page: 1639 year: 2001 ident: 2023072603015268900_bib24 article-title: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia publication-title: J. Exp. Med. doi: 10.1084/jem.194.11.1639 contributor: fullname: Rosenwald – volume: 117 start-page: 563 year: 2011 ident: 2023072603015268900_bib15 article-title: The lymph node microenvironment promotes B-cell receptor signaling, NF-κB activation, and tumor proliferation in chronic lymphocytic leukemia publication-title: Blood. doi: 10.1182/blood-2010-05-284984 contributor: fullname: Herishanu – volume: 459 start-page: 717 year: 2009 ident: 2023072603015268900_bib8 article-title: Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphoma publication-title: Nature. doi: 10.1038/nature07968 contributor: fullname: Compagno – volume: 38 start-page: e164 year: 2010 ident: 2023072603015268900_bib34 article-title: ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkq603 contributor: fullname: Wang – volume: 1 start-page: e74 year: 2014 ident: 2023072603015268900_bib4 article-title: Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study publication-title: The Lancet Haematology. doi: 10.1016/S2352-3026(14)00005-2 contributor: fullname: Baliakas – volume: 27 start-page: 2196 year: 2013 ident: 2023072603015268900_bib33 article-title: Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2 publication-title: Leukemia. doi: 10.1038/leu.2013.98 contributor: fullname: Strefford – volume: 50 start-page: 363 year: 1999 ident: 2023072603015268900_bib29 article-title: Staphylococcus aureus Cowan strain 1 activation of B-chronic lymphocytic leukaemia cells augments the response to CD40 stimulation publication-title: Scand. J. Immunol. doi: 10.1046/j.1365-3083.1999.00604.x contributor: fullname: Söderberg – volume: 46 start-page: 329 year: 2014 ident: 2023072603015268900_bib13 article-title: Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma publication-title: Nat. Genet. doi: 10.1038/ng.2900 contributor: fullname: Gunawardana – volume: 192 start-page: 3121 year: 2014 ident: 2023072603015268900_bib2 article-title: IκBε is a key regulator of B cell expansion by providing negative feedback on cRel and RelA in a stimulus-specific manner publication-title: J. Immunol. doi: 10.4049/jimmunol.1302351 contributor: fullname: Alves |
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| Snippet | NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we... Mansouri et al. applied targeted deep sequencing to identify mutations within NF- Kappa B core complex genes in CLL. NFKBIE, the gene encoding the inhibitory I... Mansouri et al. applied targeted deep sequencing to identify mutations within NF-κB core complex genes in CLL. NFKBIE , the gene encoding the inhibitory IκBε... NF-kappa B is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we... |
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| SubjectTerms | Basic Medicine Brief Definitive Report Cell and Molecular Biology Cell Nucleus - metabolism Cell Survival Cell- och molekylärbiologi Chromosome Aberrations Clinical Medicine Cohort Studies Cytoplasm - metabolism DNA Mutational Analysis Frameshift Mutation Gene Deletion Gene Expression Profiling Gene Expression Regulation, Leukemic Hematologi Hematology Humans I-kappa B Kinase - genetics I-kappa B Kinase - physiology Klinisk medicin Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Lymphoma, B-Cell - metabolism Lymphoma, B-Cell, Marginal Zone - metabolism Lymphoma, Mantle-Cell - metabolism Medical and Health Sciences Medicin och hälsovetenskap Medicinska och farmaceutiska grundvetenskaper NF-kappa B - metabolism Oligonucleotide Array Sequence Analysis Receptors, Antigen, B-Cell - metabolism Signal Transduction Treatment Outcome |
| Title | Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia |
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