5 results on '"Gentner-Göbel, Eva"'
Search Results
2. B cell receptor isotypes differentially associate with cell signaling, kinetics, and outcome in chronic lymphocytic leukemia
- Author
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Mazzarello, Andrea N., primary, Gentner-Göbel, Eva, additional, Dühren-von Minden, Marcus, additional, Tarasenko, Tatyana N., additional, Nicolò, Antonella, additional, Ferrer, Gerardo, additional, Vergani, Stefano, additional, Liu, Yun, additional, Bagnara, Davide, additional, Rai, Kanti R., additional, Burger, Jan A., additional, McGuire, Peter J., additional, Maity, Palash C., additional, Jumaa, Hassan, additional, and Chiorazzi, Nicholas, additional
- Published
- 2022
- Full Text
- View/download PDF
3. 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
4. IGLV3-21 * 01is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling
- Author
-
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
5. IGLV3-21 * 01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling.
- Author
-
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
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