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Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL

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Harvard

Agathangelidis, A, Chatzidimitriou, A, Gemenetzi, K, Giudicelli, V, Karypidou, M, Plevova, K, Davis, ZA, Yan, X-J, Jeromin, S, Schneider, C, Pedersen, LB, Tschumper, R, Sutton, LA, Baliakas, P, Scarfò, L, van Gastel, EJ, Armand, M, Tausch, E, Biderman, B, Baer, C, Bagnara, D, Navarro, A, de Septenville, A, Guido, V, Mitterbauer-Hohendanner, G, Dimovski, A, Brieghel, C, Lawless, S, Meggendorfer, M, Stranska, K, Ritgen, M, Facco, M, Tresoldi, C, Visentin, A, Patriarca, A, Catherwood, M, Bonello, L, Sudarikov, A, Vanura, K, Roumelioti, M, Skuhrova Francova, H, Moysiadis, T, Veronese, SM, Giannopoulos, K, Mansouri, L, Karan-Djurasevic, T, Sandaltzopoulos, R, Bödör, C, Fais, F, Kater, AP, Panovska-Stavridis, I, Rossi, D, Alshemmari, S, Panagiotidis, P, Costeas, PA, Espinet, B, Antic, D, Foroni, L, Montillo, M, Trentin, L, Stavroyianni, N, Gaidano, G, Francia di Celle, P, Niemann, CU, Campo, E, Anagnostopoulos, A, Pott, C, Fischer, K, Hallek, M, Oscier, DG, Stilgenbauer, S, Haferlach, C, Jelinek, DF, Chiorazzi, N, Pospisilova, S, Lefranc, M-P, Kossida, S, Langerak, AW, Belessi, C, Davi, F, Rosenquist, R, Ghia, P & Stamatopoulos, K 2021, 'Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL', Blood, vol. 137, no. 10, pp. 1365-1376. https://doi.org/10.1182/blood.2020007039

APA

Agathangelidis, A., Chatzidimitriou, A., Gemenetzi, K., Giudicelli, V., Karypidou, M., Plevova, K., Davis, Z. A., Yan, X-J., Jeromin, S., Schneider, C., Pedersen, L. B., Tschumper, R., Sutton, L. A., Baliakas, P., Scarfò, L., van Gastel, E. J., Armand, M., Tausch, E., Biderman, B., ... Stamatopoulos, K. (2021). Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood, 137(10), 1365-1376. https://doi.org/10.1182/blood.2020007039

CBE

Agathangelidis A, Chatzidimitriou A, Gemenetzi K, Giudicelli V, Karypidou M, Plevova K, Davis ZA, Yan X-J, Jeromin S, Schneider C, Pedersen LB, Tschumper R, Sutton LA, Baliakas P, Scarfò L, van Gastel EJ, Armand M, Tausch E, Biderman B, Baer C, Bagnara D, Navarro A, de Septenville A, Guido V, Mitterbauer-Hohendanner G, Dimovski A, Brieghel C, Lawless S, Meggendorfer M, Stranska K, Ritgen M, Facco M, Tresoldi C, Visentin A, Patriarca A, Catherwood M, Bonello L, Sudarikov A, Vanura K, Roumelioti M, Skuhrova Francova H, Moysiadis T, Veronese SM, Giannopoulos K, Mansouri L, Karan-Djurasevic T, Sandaltzopoulos R, Bödör C, Fais F, Kater AP, Panovska-Stavridis I, Rossi D, Alshemmari S, Panagiotidis P, Costeas PA, Espinet B, Antic D, Foroni L, Montillo M, Trentin L, Stavroyianni N, Gaidano G, Francia di Celle P, Niemann CU, Campo E, Anagnostopoulos A, Pott C, Fischer K, Hallek M, Oscier DG, Stilgenbauer S, Haferlach C, Jelinek DF, Chiorazzi N, Pospisilova S, Lefranc M-P, Kossida S, Langerak AW, Belessi C, Davi F, Rosenquist R, Ghia P, Stamatopoulos K. 2021. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. 137(10):1365-1376. https://doi.org/10.1182/blood.2020007039

MLA

Vancouver

Agathangelidis A, Chatzidimitriou A, Gemenetzi K, Giudicelli V, Karypidou M, Plevova K et al. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. 2021 Mar 11;137(10):1365-1376. https://doi.org/10.1182/blood.2020007039

Author

Agathangelidis, Andreas ; Chatzidimitriou, Anastasia ; Gemenetzi, Katerina ; Giudicelli, Veronique ; Karypidou, Maria ; Plevova, Karla ; Davis, Zadie A ; Yan, Xiao-Jie ; Jeromin, Sabine ; Schneider, Christof ; Pedersen, Lone Bredo ; Tschumper, Renee ; Sutton, Lesley A ; Baliakas, Panagiotis ; Scarfò, Lydia ; van Gastel, Ellen J ; Armand, Marine ; Tausch, Eugen ; Biderman, Bella ; Baer, Constance ; Bagnara, Davide ; Navarro, Alba ; de Septenville, Anne ; Guido, Valentina ; Mitterbauer-Hohendanner, Gerlinde ; Dimovski, Aleksandar ; Brieghel, Christian ; Lawless, Sarah ; Meggendorfer, Manja ; Stranska, Kamila ; Ritgen, Matthias ; Facco, Monica ; Tresoldi, Cristina ; Visentin, Andrea ; Patriarca, Andrea ; Catherwood, Mark ; Bonello, Lisa ; Sudarikov, Andrey ; Vanura, Katrina ; Roumelioti, Maria ; Skuhrova Francova, Hana ; Moysiadis, Theodoros ; Veronese, Silvio M ; Giannopoulos, Krzysztof ; Mansouri, Larry ; Karan-Djurasevic, Teodora ; Sandaltzopoulos, Raphael ; Bödör, Csaba ; Fais, Franco ; Kater, Arnon P ; Panovska-Stavridis, Irina ; Rossi, Davide ; Alshemmari, Salem ; Panagiotidis, Panagiotis ; Costeas, Paul A ; Espinet, Blanca ; Antic, Darko ; Foroni, Letizia ; Montillo, Marco ; Trentin, Livio ; Stavroyianni, Niki ; Gaidano, Gianluca ; Francia di Celle, Paola ; Niemann, Carsten Utoft ; Campo, Elías ; Anagnostopoulos, Achilles ; Pott, Christiane ; Fischer, Kirsten ; Hallek, Michael ; Oscier, David Graham ; Stilgenbauer, Stephan ; Haferlach, Claudia ; Jelinek, Diane F ; Chiorazzi, Nicholas ; Pospisilova, Sarka ; Lefranc, Marie-Paule ; Kossida, Sofia ; Langerak, Anton W ; Belessi, Chrysoula ; Davi, Frederic ; Rosenquist, Richard ; Ghia, Paolo ; Stamatopoulos, Kostas. / Higher-order connections between stereotyped subsets : implications for improved patient classification in CLL. In: Blood. 2021 ; Vol. 137, No. 10. pp. 1365-1376.

Bibtex

@article{7eac837db19345b3a0c70a9dcc95f571,
title = "Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL",
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.",
author = "Andreas Agathangelidis and Anastasia Chatzidimitriou and Katerina Gemenetzi and Veronique Giudicelli and Maria Karypidou and Karla Plevova and Davis, {Zadie A} and Xiao-Jie Yan and Sabine Jeromin and Christof Schneider and Pedersen, {Lone Bredo} and Renee Tschumper and Sutton, {Lesley A} and Panagiotis Baliakas and Lydia Scarf{\`o} and {van Gastel}, {Ellen J} and Marine Armand and Eugen Tausch and Bella Biderman and Constance Baer and Davide Bagnara and Alba Navarro and {de Septenville}, Anne and Valentina Guido and Gerlinde Mitterbauer-Hohendanner and Aleksandar Dimovski and Christian Brieghel and Sarah Lawless and Manja Meggendorfer and Kamila Stranska and Matthias Ritgen and Monica Facco and Cristina Tresoldi and Andrea Visentin and Andrea Patriarca and Mark Catherwood and Lisa Bonello and Andrey Sudarikov and Katrina Vanura and Maria Roumelioti and {Skuhrova Francova}, Hana and Theodoros Moysiadis and Veronese, {Silvio M} and Krzysztof Giannopoulos and Larry Mansouri and Teodora Karan-Djurasevic and Raphael Sandaltzopoulos and Csaba B{\"o}d{\"o}r and Franco Fais and Kater, {Arnon P} and Irina Panovska-Stavridis and Davide Rossi and Salem Alshemmari and Panagiotis Panagiotidis and Costeas, {Paul A} and Blanca Espinet and Darko Antic and Letizia Foroni and Marco Montillo and Livio Trentin and Niki Stavroyianni and Gianluca Gaidano and {Francia di Celle}, Paola and Niemann, {Carsten Utoft} and El{\'i}as Campo and Achilles Anagnostopoulos and Christiane Pott and Kirsten Fischer and Michael Hallek and Oscier, {David Graham} and Stephan Stilgenbauer and Claudia Haferlach and Jelinek, {Diane F} and Nicholas Chiorazzi and Sarka Pospisilova and Marie-Paule Lefranc and Sofia Kossida and Langerak, {Anton W} and Chrysoula Belessi and Frederic Davi and Richard Rosenquist and Paolo Ghia and Kostas Stamatopoulos",
note = "{\textcopyright} 2021 by The American Society of Hematology.",
year = "2021",
month = mar,
day = "11",
doi = "10.1182/blood.2020007039",
language = "English",
volume = "137",
pages = "1365--1376",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

RIS

TY - JOUR

T1 - Higher-order connections between stereotyped subsets

T2 - implications for improved patient classification in CLL

AU - Agathangelidis, Andreas

AU - Chatzidimitriou, Anastasia

AU - Gemenetzi, Katerina

AU - Giudicelli, Veronique

AU - Karypidou, Maria

AU - Plevova, Karla

AU - Davis, Zadie A

AU - Yan, Xiao-Jie

AU - Jeromin, Sabine

AU - Schneider, Christof

AU - Pedersen, Lone Bredo

AU - Tschumper, Renee

AU - Sutton, Lesley A

AU - Baliakas, Panagiotis

AU - Scarfò, Lydia

AU - van Gastel, Ellen J

AU - Armand, Marine

AU - Tausch, Eugen

AU - Biderman, Bella

AU - Baer, Constance

AU - Bagnara, Davide

AU - Navarro, Alba

AU - de Septenville, Anne

AU - Guido, Valentina

AU - Mitterbauer-Hohendanner, Gerlinde

AU - Dimovski, Aleksandar

AU - Brieghel, Christian

AU - Lawless, Sarah

AU - Meggendorfer, Manja

AU - Stranska, Kamila

AU - Ritgen, Matthias

AU - Facco, Monica

AU - Tresoldi, Cristina

AU - Visentin, Andrea

AU - Patriarca, Andrea

AU - Catherwood, Mark

AU - Bonello, Lisa

AU - Sudarikov, Andrey

AU - Vanura, Katrina

AU - Roumelioti, Maria

AU - Skuhrova Francova, Hana

AU - Moysiadis, Theodoros

AU - Veronese, Silvio M

AU - Giannopoulos, Krzysztof

AU - Mansouri, Larry

AU - Karan-Djurasevic, Teodora

AU - Sandaltzopoulos, Raphael

AU - Bödör, Csaba

AU - Fais, Franco

AU - Kater, Arnon P

AU - Panovska-Stavridis, Irina

AU - Rossi, Davide

AU - Alshemmari, Salem

AU - Panagiotidis, Panagiotis

AU - Costeas, Paul A

AU - Espinet, Blanca

AU - Antic, Darko

AU - Foroni, Letizia

AU - Montillo, Marco

AU - Trentin, Livio

AU - Stavroyianni, Niki

AU - Gaidano, Gianluca

AU - Francia di Celle, Paola

AU - Niemann, Carsten Utoft

AU - Campo, Elías

AU - Anagnostopoulos, Achilles

AU - Pott, Christiane

AU - Fischer, Kirsten

AU - Hallek, Michael

AU - Oscier, David Graham

AU - Stilgenbauer, Stephan

AU - Haferlach, Claudia

AU - Jelinek, Diane F

AU - Chiorazzi, Nicholas

AU - Pospisilova, Sarka

AU - Lefranc, Marie-Paule

AU - Kossida, Sofia

AU - Langerak, Anton W

AU - Belessi, Chrysoula

AU - Davi, Frederic

AU - Rosenquist, Richard

AU - Ghia, Paolo

AU - Stamatopoulos, Kostas

N1 - © 2021 by The American Society of Hematology.

PY - 2021/3/11

Y1 - 2021/3/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85102607193&partnerID=8YFLogxK

U2 - 10.1182/blood.2020007039

DO - 10.1182/blood.2020007039

M3 - Journal article

C2 - 32992344

VL - 137

SP - 1365

EP - 1376

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -

ID: 62290906