TY  - JOUR
AU  - Agathangelidis, Andreas
AU  - Chatzidimitriou, Anastasia
AU  - Gemenetzi, Katerina
AU  - Giudicelli, Veronique
AU  - Karypidou, Maria
AU  - Plevova, Karla
AU  - Davis, Zadie
AU  - Yan, Xiao-Jie
AU  - Jeromin, Sabine
AU  - Schneider, Christof
AU  - Pedersen, Lone Bredo
AU  - Tschumper, Renee C.
AU  - Sutton, Lesley-Ann
AU  - Baliakas, Panagiotis
AU  - Scarfo, 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 Langlois
AU  - Guido, Valentina
AU  - Mitterbauer-Hohendanner, Gerlinde
AU  - Dimovski, Aleksandar
AU  - Brieghel, Christian
AU  - Lawless, Sarah
AU  - Meggendorfer, Manja
AU  - Brazdilova, 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  - Francova, Hana Skuhrova
AU  - Moysiadis, Theodoros
AU  - Veronese, Silvio
AU  - Giannopoulos, Krzysztof
AU  - Mansouri, Larry
AU  - Karan-Đurašević, Teodora
AU  - Sandaltzopoulos, Raphael
AU  - Bodor, Csaba
AU  - Fais, Franco
AU  - Kater, Arnon
AU  - Panovska, Irina
AU  - Rossi, Davide
AU  - Alshemmari, Salem
AU  - Panagiotidis, Panagiotis
AU  - Costeas, Paul
AU  - Espinet, Blanca
AU  - Antić, Darko
AU  - Foroni, Letizia
AU  - Montillo, Marco
AU  - Trentin, Livio
AU  - Stavroyianni, Niki
AU  - Gaidano, Gianluca
AU  - di Celle, Paola Francia
AU  - Niemann, Carsten
AU  - Campo, Elias
AU  - Anagnostopoulos, Achilles
AU  - Pott, Christiane
AU  - Fischer, Kirsten
AU  - Hallek, Michael
AU  - Oscier, David
AU  - Stilgenbauer, Stephan
AU  - Haferlach, Claudia
AU  - Jelinek, Diane
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
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1427
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.
PB  - Amer Soc Hematology, Washington
T2  - Blood
T1  - Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL
EP  - 1376
IS  - 10
SP  - 1365
VL  - 137
DO  - 10.1182/blood.2020007039
ER  - 

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

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

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

Agathangelidis, Andreas, Chatzidimitriou, Anastasia, Gemenetzi, Katerina, Giudicelli, Veronique, Karypidou, Maria, Plevova, Karla, 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, Lawless, Sarah, Meggendorfer, Manja, Brazdilova, Kamila, Ritgen, Matthias, Facco, Monica, Tresoldi, Cristina, Visentin, Andrea, Patriarca, Andrea, Catherwood, Mark, Bonello, Lisa, Sudarikov, Andrey, Vanura, Katrina, Roumelioti, Maria, Francova, Hana Skuhrova, Moysiadis, Theodoros, Veronese, Silvio, Giannopoulos, Krzysztof, Mansouri, Larry, Karan-Đurašević, Teodora, Sandaltzopoulos, Raphael, Bodor, Csaba, Fais, Franco, Kater, Arnon, Panovska, Irina, Rossi, Davide, Alshemmari, Salem, Panagiotidis, Panagiotis, Costeas, Paul, Espinet, Blanca, Antić, Darko, Foroni, Letizia, Montillo, Marco, Trentin, Livio, Stavroyianni, Niki, Gaidano, Gianluca, di Celle, Paola Francia, Niemann, Carsten, 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, Stamatopoulos, Kostas, "Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL" in Blood, 137, no. 10 (2021):1365-1376,
https://doi.org/10.1182/blood.2020007039 . .