Agathangelidis, Andreas ORCID: 0000-0002-8467-7945, Chatzidimitriou, Anastasia, Gemenetzi, Katerina, Giudicelli, Veronique, Karypidou, Maria, Plevova, Karla ORCID: 0000-0002-6148-8877, Davis, Zadie, Yan, Xiao-Jie, Jeromin, Sabine, Schneider, Christof, Pedersen, Lone Bredo, Tschumper, Renee C., Sutton, Lesley-Ann, Baliakas, Panagiotis, Scarfo, Lydia, van Gastel, Ellen J., Armand, Marine, Tausch, Eugen, Biderman, Bella, Baer, Constance, Bagnara, Davide, Navarro, Alba, de Septenville, Anne Langlois, Guido, Valentina, Mitterbauer-Hohendanner, Gerlinde, Dimovski, Aleksandar, Brieghel, Christian ORCID: 0000-0002-1816-8106, Lawless, Sarah, Meggendorfer, Manja, Brazdilova, Kamila, Ritgen, Matthias, Facco, Monica, Tresoldi, Cristina, Visentin, Andrea ORCID: 0000-0003-0271-7200, Patriarca, Andrea ORCID: 0000-0003-4415-2906, Catherwood, Mark, Bonello, Lisa, Sudarikov, Andrey ORCID: 0000-0001-9463-9187, Vanura, Katrina, Roumelioti, Maria, Francova, Hana Skuhrova, Moysiadis, Theodoros ORCID: 0000-0003-1673-196X, Veronese, Silvio, Giannopoulos, Krzysztof, Mansouri, Larry, Karan-Djurasevic, Teodora, Sandaltzopoulos, Raphael, Bodor, Csaba, Fais, Franco ORCID: 0000-0002-6643-7083, Kater, Arnon, Panovska, Irina, Rossi, Davide, Alshemmari, Salem ORCID: 0000-0002-5597-5839, Panagiotidis, Panagiotis, Costeas, Paul, Espinet, Blanca ORCID: 0000-0002-4294-8145, Antic, Darko, Foroni, Letizia, Montillo, Marco, Trentin, Livio, Stavroyianni, Niki, Gaidano, Gianluca ORCID: 0000-0002-4681-0151, di Celle, Paola Francia, Niemann, Carsten ORCID: 0000-0001-9880-5242, Campo, Elias, Anagnostopoulos, Achilles, Pott, Christiane, Fischer, Kirsten, Hallek, Michael, Oscier, David, Stilgenbauer, Stephan, Haferlach, Claudia, Jelinek, Diane, Chiorazzi, Nicholas, Pospisilova, Sarka, Lefranc, Marie-Paule, Kossida, Sofia, Langerak, Anton W., Belessi, Chrysoula, Davi, Frederic, Rosenquist, Richard, Ghia, Paolo and Stamatopoulos, Kostas ORCID: 0000-0001-8529-640X (2021). Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood, 137 (10). S. 1365 - 1377. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed satellites, were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Agathangelidis, AndreasUNSPECIFIEDorcid.org/0000-0002-8467-7945UNSPECIFIED
Chatzidimitriou, AnastasiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gemenetzi, KaterinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giudicelli, VeroniqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karypidou, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plevova, KarlaUNSPECIFIEDorcid.org/0000-0002-6148-8877UNSPECIFIED
Davis, ZadieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yan, Xiao-JieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jeromin, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pedersen, Lone BredoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tschumper, Renee C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutton, Lesley-AnnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baliakas, PanagiotisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scarfo, LydiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Gastel, Ellen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Armand, MarineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tausch, EugenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biderman, BellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baer, ConstanceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bagnara, DavideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Navarro, AlbaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Septenville, Anne LangloisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guido, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitterbauer-Hohendanner, GerlindeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dimovski, AleksandarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brieghel, ChristianUNSPECIFIEDorcid.org/0000-0002-1816-8106UNSPECIFIED
Lawless, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meggendorfer, ManjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brazdilova, KamilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ritgen, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Facco, MonicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tresoldi, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Visentin, AndreaUNSPECIFIEDorcid.org/0000-0003-0271-7200UNSPECIFIED
Patriarca, AndreaUNSPECIFIEDorcid.org/0000-0003-4415-2906UNSPECIFIED
Catherwood, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonello, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sudarikov, AndreyUNSPECIFIEDorcid.org/0000-0001-9463-9187UNSPECIFIED
Vanura, KatrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roumelioti, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Francova, Hana SkuhrovaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moysiadis, TheodorosUNSPECIFIEDorcid.org/0000-0003-1673-196XUNSPECIFIED
Veronese, SilvioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giannopoulos, KrzysztofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mansouri, LarryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karan-Djurasevic, TeodoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sandaltzopoulos, RaphaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bodor, CsabaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fais, FrancoUNSPECIFIEDorcid.org/0000-0002-6643-7083UNSPECIFIED
Kater, ArnonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Panovska, IrinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rossi, DavideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alshemmari, SalemUNSPECIFIEDorcid.org/0000-0002-5597-5839UNSPECIFIED
Panagiotidis, PanagiotisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Costeas, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espinet, BlancaUNSPECIFIEDorcid.org/0000-0002-4294-8145UNSPECIFIED
Antic, DarkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foroni, LetiziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montillo, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trentin, LivioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stavroyianni, NikiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaidano, GianlucaUNSPECIFIEDorcid.org/0000-0002-4681-0151UNSPECIFIED
di Celle, Paola FranciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niemann, CarstenUNSPECIFIEDorcid.org/0000-0001-9880-5242UNSPECIFIED
Campo, EliasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anagnostopoulos, AchillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pott, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, KirstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oscier, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haferlach, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jelinek, DianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chiorazzi, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pospisilova, SarkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lefranc, Marie-PauleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kossida, SofiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langerak, Anton W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Belessi, ChrysoulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davi, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenquist, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghia, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stamatopoulos, KostasUNSPECIFIEDorcid.org/0000-0001-8529-640XUNSPECIFIED
URN: urn:nbn:de:hbz:38-608097
DOI: 10.1182/blood.2020007039
Journal or Publication Title: Blood
Volume: 137
Number: 10
Page Range: S. 1365 - 1377
Date: 2021
Publisher: AMER SOC HEMATOLOGY
Place of Publication: WASHINGTON
ISSN: 1528-0020
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL RECEPTOR; GENE-EXPRESSION PROFILES; V-H; DISTINCT; ANTIBODIES; PATTERNS; IMMUNOGLOBULINS; RECOGNITION; REPERTOIREMultiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60809

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