8 results on '"Somers, Sebastiaan F."'
Search Results
2. IGLV3-21*01 is an inherited risk factor for CLL throughthe acquisition of a single-point mutation enablingautonomous BCR signaling
- Author
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Maity, Palash C., Bilal, Mayas, Koning, Marvyn T., Young, Marc, Van Bergen, Cornelis A. M., Renna, Valerio, Nicolo, Antonella, Datta, Moumita, Gentner-Göbel, Eva, Barendse, Rob S., Somers, Sebastiaan F., De Groen, Ruben A. L., Vermaat, Joost S. P., Steinbrecher, Daniela, Schneider, Christof, Tausch, Eugen, Bittolo, Tamara, Bomben, Riccardo, Mazzarello, Andrea Nicola, Del Poeta, Giovanni, Kroes, Wilma G. M., Van Wezel, J. Tom, Imkeller, Katharina, Busse, Christian E., Degano, Massimo, Bakchoul, Tamam, Schulz, Axel Ronald, Mei, Henrik, Ghia, Paolo, Kotta, Konstantia, Stamatopoulos, Kostas, Wardemann, Hedda, Zucchetto, Antonella, Chiorazzi, Nicholas, Gattei, Valter, Stilgenbauer, Stephan, Veelken, Hendrik, and Jumaa, Hassan
- Subjects
GENES ,Survival ,Überleben ,Receptors, Antigen, B-Cell ,Immunoglobulins ,Prognose ,Immunophenotyping ,13Q14 ,DDC 570 / Life sciences ,Antigens, CD ,ddc:570 ,chronic lymphocytic leukemia (CLL) ,LENGTH ,ddc:610 ,PROGNOSTIC INDEX ,immunoglobulin allele IGLV3-21*01 ,autonomous BCR signaling ,Immunogenetic phenomena ,Prognosis ,B-Lymphozyten-Rezeptor ,Leukemia, Lymphocytic, Chronic, B-Cell ,DELETIONS ,Antigen CD38 ,CD38 EXPRESSION ,IMMUNOGLOBULIN HEAVY ,Immunglobuline ,Chronisch-lymphatische Leukämie ,B cell antigen receptor (BCR) ,DDC 610 / Medicine & health - Abstract
The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementarity-determining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21–derived heavy chains (HCs) with IGLV3-21–derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21R110), we show that IGLV3-21R110–expressing CLL represents a distinct subset with poor prognosis independent of IGHV mutations. Compared with other alleles, only IGLV3-21*01 facilitates effective homotypic BCR–BCR interaction that results in autonomous, oncogenic BCR signaling after acquiring R110 as a single-point mutation. Presumably, this mutation acts as a standalone driver that transforms IGLV3-21*01–expressing B cells to develop CLL. Thus, we propose to expand the conventional definition of CLL subset 2 to subset 2L by including all IGLV3-21R110–expressing CLL cases regardless of IGHV mutational status. Moreover, the generation of monoclonal antibodies recognizing IGLV3-21 or mutated IGLV3-21R110 facilitates the recognition of B cells carrying this mutation in CLL patients or healthy donors., publishedVersion
- Published
- 2020
3. IGLV3-21 * 01is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling
- Author
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Maity, Palash C., primary, Bilal, Mayas, additional, Koning, Marvyn T., additional, Young, Marc, additional, van Bergen, Cornelis A. M., additional, Renna, Valerio, additional, Nicolò, Antonella, additional, Datta, Moumita, additional, Gentner-Göbel, Eva, additional, Barendse, Rob S., additional, Somers, Sebastiaan F., additional, de Groen, Ruben A. L., additional, Vermaat, Joost S. P., additional, Steinbrecher, Daniela, additional, Schneider, Christof, additional, Tausch, Eugen, additional, Bittolo, Tamara, additional, Bomben, Riccardo, additional, Mazzarello, Andrea Nicola, additional, del Poeta, Giovanni, additional, Kroes, Wilma G. M., additional, van Wezel, J. Tom, additional, Imkeller, Katharina, additional, Busse, Christian E., additional, Degano, Massimo, additional, Bakchoul, Tamam, additional, Schulz, Axel Ronald, additional, Mei, Henrik, additional, Ghia, Paolo, additional, Kotta, Konstantia, additional, Stamatopoulos, Kostas, additional, Wardemann, Hedda, additional, Zucchetto, Antonella, additional, Chiorazzi, Nicholas, additional, Gattei, Valter, additional, Stilgenbauer, Stephan, additional, Veelken, Hendrik, additional, and Jumaa, Hassan, additional
- Published
- 2020
- Full Text
- View/download PDF
4. High prevalence of MYD88 and CD79B mutations in intravascular large B-cell lymphoma
- Author
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Schrader, Anne M.R., Jansen, Patty M., Willemze, Rein, Vermeer, Maarten H., Cleton-Jansen, Anne-Marie, Somers, Sebastiaan F., Veelken, Hendrik, van Eijk, Ronald, Kraan, Willem, Kersten, Marie José, van den Brand, Michiel, Stevens, Wendy B.C., de Jong, Daphne, Abdul Hamid, Myrurgia, Tanis, Bea C., Posthuma, Eduardus F.M., Nijland, Marcel, Diepstra, Arjan, Pals, Steven T., Cleven, Arjen H.G., and Vermaat, Joost S.P.
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- 2018
- Full Text
- View/download PDF
5. MYD88 mutations identify a molecular subgroup of diffuse large B-cell lymphoma with an unfavorable prognosis
- Author
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Vermaat, Joost S., primary, Somers, Sebastiaan F., additional, de Wreede, Liesbeth C., additional, Kraan, Willem, additional, de Groen, Ruben A.L., additional, Schrader, Anne M. R., additional, Kerver, Emile D., additional, Scheepstra, Cornelis G., additional, Berenschot, Henriëtte, additional, Deenik, Wendy, additional, Wegman, Jurgen, additional, Broers, Rianne, additional, de Boer, Jan-Paul D., additional, Nijland, Marcel, additional, van Wezel, Tom, additional, Veelken, Hendrik, additional, Spaargaren, Marcel, additional, Cleven, Arjen H., additional, Kersten, Marie José, additional, and Pals, Steven T., additional
- Published
- 2019
- Full Text
- View/download PDF
6. High prevalence of MYD88and CD79Bmutations in intravascular large B-cell lymphoma
- Author
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Schrader, Anne M.R., Jansen, Patty M., Willemze, Rein, Vermeer, Maarten H., Cleton-Jansen, Anne-Marie, Somers, Sebastiaan F., Veelken, Hendrik, van Eijk, Ronald, Kraan, Willem, Kersten, Marie José, van den Brand, Michiel, Stevens, Wendy B.C., de Jong, Daphne, Abdul Hamid, Myrurgia, Tanis, Bea C., Posthuma, Eduardus F.M., Nijland, Marcel, Diepstra, Arjan, Pals, Steven T., Cleven, Arjen H.G., and Vermaat, Joost S.P.
- Published
- 2018
- Full Text
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7. IGLV3-21 * 01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling.
- Author
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Maity PC, Bilal M, Koning MT, Young M, van Bergen CAM, Renna V, Nicolò A, Datta M, Gentner-Göbel E, Barendse RS, Somers SF, de Groen RAL, Vermaat JSP, Steinbrecher D, Schneider C, Tausch E, Bittolo T, Bomben R, Mazzarello AN, Del Poeta G, Kroes WGM, van Wezel JT, Imkeller K, Busse CE, Degano M, Bakchoul T, Schulz AR, Mei H, Ghia P, Kotta K, Stamatopoulos K, Wardemann H, Zucchetto A, Chiorazzi N, Gattei V, Stilgenbauer S, Veelken H, and Jumaa H
- Subjects
- B-Lymphocytes immunology, Cohort Studies, Complementarity Determining Regions genetics, Complementarity Determining Regions immunology, Genetic Predisposition to Disease, Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin Heavy Chains immunology, Immunoglobulin lambda-Chains immunology, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Point Mutation, Receptors, Antigen, B-Cell genetics, Immunoglobulin lambda-Chains genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Receptors, Antigen, B-Cell immunology
- Abstract
The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementarity-determining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21-derived heavy chains (HCs) with IGLV3-21-derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21
R110 ), we show that IGLV3-21R110 -expressing CLL represents a distinct subset with poor prognosis independent of IGHV mutations. Compared with other alleles, only IGLV3-21 * 01 facilitates effective homotypic BCR-BCR interaction that results in autonomous, oncogenic BCR signaling after acquiring R110 as a single-point mutation. Presumably, this mutation acts as a standalone driver that transforms IGLV3-21 * 01 -expressing B cells to develop CLL. Thus, we propose to expand the conventional definition of CLL subset 2 to subset 2L by including all IGLV3-21R110 -expressing CLL cases regardless of IGHV mutational status. Moreover, the generation of monoclonal antibodies recognizing IGLV3-21 or mutated IGLV3-21R110 facilitates the recognition of B cells carrying this mutation in CLL patients or healthy donors., Competing Interests: Competing interest statement: H.J. is a cofounder of AVA LifeScience GmbH that has filed patents on antibodies recognizing structures involved in autonomous BCR signaling., (Copyright © 2020 the Author(s). Published by PNAS.)- Published
- 2020
- Full Text
- View/download PDF
8. MYD88 mutations identify a molecular subgroup of diffuse large B-cell lymphoma with an unfavorable prognosis.
- Author
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Vermaat JS, Somers SF, de Wreede LC, Kraan W, de Groen RAL, Schrader AMR, Kerver ED, Scheepstra CG, Berenschot H, Deenik W, Wegman J, Broers R, de Boer JD, Nijland M, van Wezel T, Veelken H, Spaargaren M, Cleven AH, Kersten MJ, and Pals ST
- Subjects
- Herpesvirus 4, Human, Humans, In Situ Hybridization, Fluorescence, Mutation, Prognosis, Epstein-Barr Virus Infections genetics, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse genetics, Myeloid Differentiation Factor 88 genetics
- Abstract
The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of MYC/BCL2/BCL6 as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in MYD88/CD79B We investigated whether MYD88/CD79B mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, MYD88/CD79B mutations were identified by allele-specific polymerase chain reaction or next-generation-sequencing, MYC/BCL2/BCL6 rearrangements were analyzed by fluorescence in situ hybridization, and EBV was studied by EBV-encoded RNA in situ hybridization. Associations of molecular features with clinicopathologic characteristics, outcome, and prognosis according to the International Prognostic Index (IPI) were investigated. MYD88 and CD79B mutations were identified in 29.6% and 12.3%, MYC, BCL2 , and BCL6 rearrangements in 10.6%, 13.6%, and 20.3%, and EBV in 11.7% of DLBCL, respectively. Prominent mutual exclusivity between EBV positivity, rearrangements, and MYD88/CD79B mutations established the value of molecular markers for the recognition of biologically distinct DLBCL subtypes. MYD88 -mutated DLBCL had a significantly inferior 5-year overall survival than wild-type MYD88 DLBCL (log-rank; P =0.019). DLBCL without any of the studied aberrations had superior overall survival compared to cases carrying ≥1 aberrancy (log-rank; P =0.010). MYD88 mutations retained their adverse prognostic impact upon adjustment for other genetic and clinical variables by multivariable analysis and improved the prognostic performance of the IPI. This study demonstrates the clinical utility of defining MYD88 -mutated DLBCL as a distinct molecular subtype with adverse prognosis. Our data call for sequence analysis of MYD88 in routine diagnostics of DLBCL to optimize classification and prognostication, and to guide the development of improved treatment strategies., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
- Full Text
- View/download PDF
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