13 results on '"Young, Emma"'
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2. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
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Mansouri, Larry, Noerenberg, Daniel, Young, Emma, Mylonas, Elena, Abdulla, Maysaa, Frick, Mareike, Asmar, Fazila, Ljungström, Viktor, Schneider, Markus, Yoshida, Kenichi, Skaftason, Aron, Pandzic, Tatjana, Gonzalez, Blanca, Tasidou, Anna, Waldhueter, Nils, Rivas-Delgado, Alfredo, Angelopoulou, Maria, Ziepert, Marita, Arends, Christopher Maximilian, Couronné, Lucile, Lenze, Dido, Baldus, Claudia D., Bastard, Christian, Okosun, Jessica, Fitzgibbon, Jude, Dörken, Bernd, Drexler, Hans G., Roos-Weil, Damien, Schmitt, Clemens A., Munch-Petersen, Helga D., Zenz, Thorsten, Hansmann, Martin-Leo, Strefford, Jonathan C., Enblad, Gunilla, Bernard, Olivier A., Ralfkiaer, Elisabeth, Erlanson, Martin, Korkolopoulou, Penelope, Hultdin, Magnus, Papadaki, Theodora, Grønbæk, Kirsten, Lopez-Guillermo, Armando, Ogawa, Seishi, Küppers, Ralf, Stamatopoulos, Kostas, Stavroyianni, Niki, Kanellis, George, Rosenwald, Andreas, Campo, Elias, Amini, Rose-Marie, Ott, German, Vassilakopoulos, Theodoros P., Hummel, Michael, Rosenquist, Richard, and Damm, Frederik
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- 2016
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3. ΝFΚΒΙΕ Deletions: A Novel Marker of Clinical Aggressiveness in Primary Mediastinal B-Cell Lymphoma
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Noerenberg*, Daniel, primary, Mansouri*, Larry, additional, Young, Emma, additional, Mareike, Frick, additional, Abdulla, Maysaa, additional, Asmar, Fazila, additional, Gonzalez-Farre, Blanca, additional, Anna, Tasidou, additional, Waldhueter, Nils, additional, Ljungström, Viktor, additional, Rivas, Alfredo, additional, Angelopoulou, Maria K., additional, Ziepert, Marita, additional, Arends, Christopher M., additional, Couronne, Lucile, additional, Lenze, Dido, additional, Baldus, Claudia D., additional, Bastard, Christian, additional, Okosun, Jessica, additional, Fitzgibbon, Jude, additional, Dörken, Bernd, additional, Drexler, Hans G., additional, Roos-Weil, Damien, additional, Schmitt, Clemens A., additional, Munch-Petersen, Helga Duverger, additional, Zenz, Thorsten, additional, Strefford, Jonathan C., additional, Enblad, Gunilla, additional, Bernard, Olivier A., additional, Ralfkiaer, Elisabeth, additional, Korkolopoulou, Penelope, additional, Hultdin, Magnus, additional, Papadaki, Theodora, additional, Grønbæk, Kirsten, additional, Lopez-Guillermo, Armando, additional, Stamatopoulos, Kostas, additional, Stavroyianni, Niki, additional, Kanellis, George, additional, Rosenwald, Andreas, additional, Campo, Elias, additional, Amini, Rose-Marie, additional, Ott, German, additional, Vassilakopoulos, Theodoros, additional, Hummel, Michael, additional, Damm**, Frederik, additional, and Rosenquist**, Richard, additional
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- 2016
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4. Tailored Approaches for Refined Prognostication in Chronic Lymphocytic Leukemia Patients with Mutated Versus Unmutated Immunoglobulin Receptors
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Baliakas, Panagiotis, primary, Moysiadis, Theodoros, additional, Hadzidimitriou, Anastasia, additional, Xochelli, Aliki, additional, Mattsson, Mattias, additional, Sutton, Lesley-Ann, additional, Minga, Eva, additional, Scarfo, Lydia, additional, Rossi, Davide, additional, Davis, Zadie, additional, Agathangelidis, Andreas, additional, Villamor, Neus, additional, Parker, Helen, additional, Kotaskova, Jana, additional, Stalika, Evangelia, additional, Plevova, Karla, additional, Mansouri, Larry, additional, Cortese, Diego, additional, Lopez, Alba Navaro, additional, Delgado, Julio, additional, Larrayoz, Marta, additional, Young, Emma, additional, Anagnostopoulos, Achilles, additional, Smedby, Karin E, additional, Juliusson, Gunnar, additional, Catherwood, Mark, additional, Strefford, Jonathan C, additional, Stavroyianni, Niki, additional, Belessi, Chrysoula, additional, Pospisilova, Sarka, additional, Oscier, David, additional, Gaidano, Gianluca, additional, Campo, Elias, additional, Ghia, Paolo, additional, Rosenquist, Richard, additional, and Stamatopoulos, on behalf of ERIC, Kostas, additional
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- 2016
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5. EGR2 Mutations in Chronic Lymphocytic Leukemia: A New Bad Player
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Noerenberg*, Daniel, primary, Young*, Emma, additional, Ljungström, Viktor, additional, Mansouri, Larry, additional, Plevova, Karla, additional, Baliakas, Panagiotis, additional, Blakemore, Stuart, additional, Rossi, Davide, additional, Clifford, Ruth, additional, Navrkalova, Veronika, additional, Sutton, Lesley-Ann, additional, Smedby, Karin E, additional, Juliusson, Gunnar, additional, Belessi, Chrysoula, additional, Panagiotidis, Panagiotis, additional, Chiorazzi, Nicholas, additional, Davi, Frederic, additional, Langerak, Anton W., additional, Schuh, Anna, additional, Gaidano, Gianluca, additional, Strefford, Jonathan C, additional, Ghia, Paolo, additional, Stamatopoulos, Kostas, additional, Pospisilova, Sarka, additional, Zenz, Thorsten, additional, Rosenquist**, Richard, additional, and Damm**, Frederik, additional
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- 2015
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6. ATM Mutations in Major Stereotyped CLL Subsets: Enrichment in Subset #2 is Associated with Unfavourable Outcome
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Navrkalova, Veronika, primary, Young, Emma, additional, Baliakas, Panagiotis, additional, Radova, Lenka, additional, Plevova, Karla, additional, Sutton, Lesley-Ann, additional, Mansouri, Larry, additional, Ljungstrom, Viktor, additional, Ntoufa, Stavroula, additional, Davis, Zadie, additional, Juliusson, Gunnar, additional, Smedby, Karin E, additional, Belessi, Chrysoula, additional, Panagiotidis, Panagiotis, additional, Davi, Frederic, additional, Langerak, Anton W., additional, Ghia, Paolo, additional, Strefford, Jonathan C, additional, Oscier, David G, additional, Stamatopoulos, Kostas, additional, Pospisilova, Sarka, additional, Rosenquist, Richard, additional, and Trbusek, Martin, additional
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- 2015
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7. Genome-Wide DNA Methylation Profiling of Chronic Lymphocytic Leukemia Subsets Carrying Stereotyped B Cell Receptors
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Rosenquist, Richard, Mansouri, Larry, Bhoi, Sujata, Castellano, Giancarlo, Sutton, Lesley Ann, Papakonstantinou, Nikos, Queirós, Ana, Baliakas, Panagiotis, Ek, Sara, Kuci Emruli, Venera, Plevova, Karla, Ntoufa, Stavroula, Davis, Zadie, Young, Emma, Goransson-Kultima, Hanna, Isaksson, Anders, Smedby, Karin E, Gaidano, Gianluca, Langerak, Anton W, Davi, Frederic, Rossi, Davide, Oscier, David, Pospisilova, Sarka, Ghia, Paolo, Campo, Elias, Stamatopoulos, Kostas, and Subero, Inaki Martin
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- 2017
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8. Recurrent Mutations within the Nfkbie gene: A Novel Mechanism for NF-κB Deregulation in Aggressive Chronic Lymphocytic Leukemia
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Mansouri, Larry, primary, Sutton, Lesley-Ann, additional, Ljungstrom, Viktor, additional, Bondza, Sina, additional, Arngarden, Linda, additional, Bhoi, Sujata, additional, Larsson, Jimmy, additional, Cortese, Diego, additional, Kalushkova, Antonia, additional, Gunnarsson, Rebeqa, additional, Young, Emma, additional, Falk-Sorqvist, Elin, additional, Plevova, Karla, additional, Muggen, Alice, additional, Yan, Xiao-Jie, additional, Sander, Birgitta, additional, Enblad, Gunilla, additional, Smedby, Karin E, additional, Juliusson, Gunnar, additional, Belessi, Chrysoula, additional, Chiorazzi, Nicholas, additional, Strefford, Jonathan C, additional, Langerak, Anton W, additional, Pospisilova, Sarka, additional, Davi, Frederic, additional, Hellstrom, Mats, additional, Jernberg Wiklund, Helena, additional, Ghia, Paolo, additional, Soderberg, Ola, additional, Stamatopoulos, Kostas, additional, Nilsson, Mats, additional, and Rosenquist, Richard, additional
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- 2014
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9. Subset-Specific Spectra of Recurrent Gene Mutations in Chronic Lymphocytic Leukemia with Stereotyped B-Cell Receptors
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Sutton, Lesley-Ann, primary, Young, Emma, additional, Baliakas, Panagiotis, additional, Hadzidimitriou, Anastasia, additional, Plevova, Karla, additional, Rossi, Davide, additional, Malcikova, Jitka, additional, Stalika, Evangelia, additional, Pedersen, Lone Bredo, additional, Agathangelidis, Andreas, additional, Davis, Zadie, additional, Mansouri, Larry, additional, Scarfò, Lydia, additional, Boudjogra, Myriam, additional, Navarro, Alba, additional, Muggen, Alice, additional, Yan, Xiao-Jie, additional, Panagiotidis, Panagiotis, additional, Chiorazzi, Nicholas, additional, Geisler, Christian, additional, Belessi, Chrysoula, additional, Campo, Elias, additional, Strefford, Jonathan C., additional, Ghia, Paolo, additional, Langerak, Anton W, additional, Oscier, David, additional, Gaidano, Gianluca, additional, Pospisilova, Sarka, additional, Davi, Frederic, additional, Stamatopoulos, Kostas, additional, and Rosenquist, Richard, additional
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- 2014
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10. Frequent NFKBIEdeletions are associated with poor outcome in primary mediastinal B-cell lymphoma
- Author
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Mansouri, Larry, Noerenberg, Daniel, Young, Emma, Mylonas, Elena, Abdulla, Maysaa, Frick, Mareike, Asmar, Fazila, Ljungström, Viktor, Schneider, Markus, Yoshida, Kenichi, Skaftason, Aron, Pandzic, Tatjana, Gonzalez, Blanca, Tasidou, Anna, Waldhueter, Nils, Rivas-Delgado, Alfredo, Angelopoulou, Maria, Ziepert, Marita, Arends, Christopher Maximilian, Couronné, Lucile, Lenze, Dido, Baldus, Claudia D., Bastard, Christian, Okosun, Jessica, Fitzgibbon, Jude, Dörken, Bernd, Drexler, Hans G., Roos-Weil, Damien, Schmitt, Clemens A., Munch-Petersen, Helga D., Zenz, Thorsten, Hansmann, Martin-Leo, Strefford, Jonathan C., Enblad, Gunilla, Bernard, Olivier A., Ralfkiaer, Elisabeth, Erlanson, Martin, Korkolopoulou, Penelope, Hultdin, Magnus, Papadaki, Theodora, Grønbæk, Kirsten, Lopez-Guillermo, Armando, Ogawa, Seishi, Küppers, Ralf, Stamatopoulos, Kostas, Stavroyianni, Niki, Kanellis, George, Rosenwald, Andreas, Campo, Elias, Amini, Rose-Marie, Ott, German, Vassilakopoulos, Theodoros P., Hummel, Michael, Rosenquist, Richard, and Damm, Frederik
- Abstract
We recently reported a truncating deletion in the NFKBIEgene, which encodes IκBε, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because preliminary data indicate enrichment of NFKBIEaberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIEdeletions 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 NFKBIEaberrations (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 with wild-type 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) and when restricting the analysis 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 NFKBIEaberrations as a common genetic event across B-cell malignancies and highlight NFKBIEdeletions as a novel poor-prognostic marker in PMBL.
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- 2016
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11. EGR2Mutations in Chronic Lymphocytic Leukemia: A New Bad Player
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Noerenberg, Daniel, Young, Emma, Ljungström, Viktor, Mansouri, Larry, Plevova, Karla, Baliakas, Panagiotis, Blakemore, Stuart, Rossi, Davide, Clifford, Ruth, Navrkalova, Veronika, Sutton, Lesley-Ann, Smedby, Karin E, Juliusson, Gunnar, Belessi, Chrysoula, Panagiotidis, Panagiotis, Chiorazzi, Nicholas, Davi, Frederic, Langerak, Anton W., Schuh, Anna, Gaidano, Gianluca, Strefford, Jonathan C, Ghia, Paolo, Stamatopoulos, Kostas, Pospisilova, Sarka, Zenz, Thorsten, Rosenquist, Richard, and Damm, Frederik
- Abstract
Recurrent mutations within EGR2, a versatile transcription factor involved in differentiation of hematopoietic cells, were recently reported in 8% of advanced-stage chronic lymphocytic leukemia (CLL) patients, where they appear to be associated with a worse outcome. EGR2 is activated through ERK phosphorylation upon B-cell receptor (BcR) stimulation, and we have previously shown that EGR2-mutated CLL patients display altered expression of EGR2down-stream target genes compared to wildtype (wt) patients, thereby pointing to a pathogenic role for EGR2mutations in dysregulating BcR signaling.
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- 2015
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12. ATMMutations in Major Stereotyped CLL Subsets: Enrichment in Subset #2 is Associated with Unfavourable Outcome
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Navrkalova, Veronika, Young, Emma, Baliakas, Panagiotis, Radova, Lenka, Plevova, Karla, Sutton, Lesley-Ann, Mansouri, Larry, Ljungstrom, Viktor, Ntoufa, Stavroula, Davis, Zadie, Juliusson, Gunnar, Smedby, Karin E, Belessi, Chrysoula, Panagiotidis, Panagiotis, Davi, Frederic, Langerak, Anton W., Ghia, Paolo, Strefford, Jonathan C, Oscier, David G, Stamatopoulos, Kostas, Pospisilova, Sarka, Rosenquist, Richard, and Trbusek, Martin
- Abstract
Chronic lymphocytic leukemia (CLL) is a paradigmatic malignancy where the interplay of cell-extrinsic and cell-intrinsic factors has a major impact on disease evolution. Indeed, extrinsic triggering, e.g. antigenic stimulation through the B-cell receptor (BcR), together with intrinsic aberrations, e.g. accumulation of genetic defects, play a major role throughout the natural history of CLL. The importance of antigen involvement is underscored by the existence of 'stereotyped' BcR in up to 30% of CLL patients. Notably, CLL patients with stereotyped BcR can be grouped into different subsets, each with a subset-biased biological and clinical profile. For instance, while the clinically aggressive subset #2 (IGHV3-21/IGLV3-21, comprising both mutated (M-CLL) and unmutated (U-CLL) IGHV genes) displays a remarkably high frequency of SF3B1mutations, subset #8, a subset with the highest risk of Richter transformation, shows a strong association with trisomy 12 and NOTCH1mutations. ATMdefects are implicated in the evolution of CLL and are associated with a dismal prognosis, however the extent to which they contribute to the genetic landscape in stereotyped subsets remains unexplored.
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- 2015
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13. Recurrent Mutations within the Nfkbiegene: A Novel Mechanism for NF-κB Deregulation in Aggressive Chronic Lymphocytic Leukemia
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Mansouri, Larry, Sutton, Lesley-Ann, Ljungstrom, Viktor, Bondza, Sina, Arngarden, Linda, Bhoi, Sujata, Larsson, Jimmy, Cortese, Diego, Kalushkova, Antonia, Gunnarsson, Rebeqa, Young, Emma, Falk-Sorqvist, Elin, Plevova, Karla, Muggen, Alice, Yan, Xiao-Jie, Sander, Birgitta, Enblad, Gunilla, Smedby, Karin E, Juliusson, Gunnar, Belessi, Chrysoula, Chiorazzi, Nicholas, Strefford, Jonathan C, Langerak, Anton W, Pospisilova, Sarka, Davi, Frederic, Hellstrom, Mats, Jernberg Wiklund, Helena, Ghia, Paolo, Soderberg, Ola, Stamatopoulos, Kostas, Nilsson, Mats, and Rosenquist, Richard
- Abstract
Dysregulated NF-κB signaling appears to be particularly important in B-cell malignancies, with recurrent mutations identified within both the canonical and non-canonical NF-κB pathways, as well as in components of the B-cell receptor (BcR) and Toll-like receptor (TLR) signaling pathways. In chronic lymphocytic leukemia (CLL), although recurrent mutations have been identified in MYD88(TLR signaling) and BIRC3(non-canonical NF-κB pathway), their frequency is low (<3%) and hence the extent to which genetic aberrations may contribute to constitutional NF-κB activation remains largely unknown. To gain further insight into this issue, we designed a HaloPlex gene panel (Agilent Technologies) and performed targeted next-generation sequencing (NGS) (HiSeq 2000/Illumina) of 18 NF-κB genes in a discovery cohort of 124 CLL patients, intentionally biased towards poor-prognostic patients with either unmutated IGHV genes or high-risk genomic aberrations. Using a conservative cutoff of >10% for the mutant allele, we identified mutations (n=35) within 30/124 (24%) patients in 14/18 NF-κB genes analyzed. IκB genes, which encode for cytoplasmic inhibitor proteins, accounted for 20/35 (57%) mutations, with IκBε (encoded by NFKBIE) mutated in 8 patients; notably, 3/8 cases carried an identical 4bp deletion within exon 1 of NFKBIE. Prompted by these findings, we proceeded to validate our findings in an independent CLL cohort (n=168) using the same methodology as above and primarily focusing on cases with poor-prognostic features. We identified 30 mutations within 28 CLL patients in 11/18 NF-κB genes analyzed. Strikingly, 13/30 mutations were found within IκBε, with 10/13 patients carrying the same 4bp NFKBIEdeletion. Notably, investigations into whether additional cases (within both the discovery and validation cohort) may harbor mutations of low clonal abundance (<10% mutant allele), led to the detection of the NFKBIEdeletion in another 18 cases. Owing to the prevalence of this 4bp deletion within the NFKBIEgene, we developed a GeneScan assay and screened an additional 312 CLL cases. Collectively, 40/604 (6.6%) CLL patients were found to carry this frame-shift deletion within the NFKBIEgene, which is in line with a recent publication reporting that 10% of Binet stage B/C patients carried this mutation (Damm et al. Cancer Discovery 2014). Remarkably, the majority of these NFKBIEmutations (16/40) were found in a subgroup of patients that expressed highly similar or stereotyped BcRs and are known to have a particularly poor outcome, denoted as subset #1. This finding thus alludes to a subset-biased acquisition and/or selection of genomic aberrations, similar to what has been reported for subset #2 and SF3B1, perhaps as a result of particular modes of BcR/antigen interaction. We utilized proximity-ligation assays to test the functional impact of the NFKBIEdeletion by investigating protein-protein interactions. This analysis revealed reduced interaction between the inhibitor IκBε and the transcription factor p65 in NFKBIE-deleted CLL cells; IκBε-knock-down shRNA experiments confirmed dysregulated apoptosis/NF-κB signaling. Finally, to assess whether the NFKBIEdeletion could also be present in other B-cell malignancies, we screened 372 mature B-cell lymphoma cases using NGS or the GeneScan assay and found the deletion in 7/136 (5.1%) mantle cell lymphomas, 3/66 (4.5%) diffuse large B-cell lymphomas and 3/170 (1.8%) splenic marginal zone lymphomas. Taken together, our analysis revealed that inactivating mutations within the NFKBIEgene lead to NF-κB activation in CLL and potentially several other B-cell-derived malignancies. Considering the central role of BcR stimulation in the natural history of CLL, the functional loss of IκBε may significantly contribute to sustained CLL cell survival and shape the disease evolution. This novel data strongly indicates that components of the NF-κB signaling pathway may be prime targets for future targeted therapies not only in CLL but also other mature B-cell lymphomas.
- Published
- 2014
- Full Text
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