Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL
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AGATHANGELIDIS, A., A. CHATZIDIMITRIOU, K. GEMENETZI, V. GIUDICELLI, M. KARYPIDOU, Karla PLEVOVÁ (203 Česká republika, domácí), Z. DAVIS, X.J. YAN, S. JEROMIN, C. SCHNEIDER, L.B. PEDERSEN, R.C. TSCHUMPER, L.A. SUTTON, P. BALIAKAS, L. SCARFO, E.J. VAN GASTEL, M. ARMAND, E. TAUSCH, B. BIDERMAN, C. BAER, D. BAGNARA, A. NAVARRO, A.L. DE SEPTENVILLE, V. GUIDO, G. MITTERBAUER-HOHENDANNER, A. DIMOVSKI, C. BRIEGHEL, S. LAWLESS, M. MEGGENDORFER, Kamila STRÁNSKÁ (203 Česká republika, domácí), M. RITGEN, M. FACCO, C. TRESOLDI, A. VISENTIN, A. PATRIARCA, M. CATHERWOOD, L. BONELLO, A. SUDARIKOV, K. VANURA, M. ROUMELIOTI, H.S. FRANCOVA, T. MOYSIADIS, S. VERONESE, K. GIANNOPOULOS, L. MANSOURI, T. KARAN-DJURASEVIC, R. SANDALTZOPOULOS, C. BODOR, F. FAIS, A. KATER, I. PANOVSKA, D. ROSSI, S. ALSHEMMARI, P. PANAGIOTIDIS, P. COSTEAS, B. ESPINET, D. ANTIC, L. FORONI, M. MONTILLO, L. TRENTIN, N. STAVROYIANNI, G. GAIDANO, P.F. DI CELLE, C. NIEMANN, E. CAMPO, A. ANAGNOSTOPOULOS, C. POTT, K. FISCHER, M. HALLEK, D. OSCIER, S. STILGENBAUER, C. HAFERLACH, D. JELINEK, N. CHIORAZZI, Šárka POSPÍŠILOVÁ (203 Česká republika, garant, domácí), M.P. LEFRANC, S. KOSSIDA, A.W. LANGERAK, Cx. BELESSI, F. DAVI, R. ROSENQUIST, P. GHIA a K. STAMATOPOULOS
Vydání
Blood, Washington DC, USA, American Society of Hematology, 2021, 0006-4971
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.
Návaznosti
LQ1601, projekt VaV
Název: CEITEC 2020 (Akronym: CEITEC2020)
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020
NV19-03-00091, projekt VaV
Název: Komplexní prognostický a prediktivní panel pro pacienty s chronickou lymfocytární leukémií: nástroj sekvenování nové generace vhodný pro klinickou praxi i studium genetického pozadí průběhu choroby
Investor: Ministerstvo zdravotnictví ČR, Comprehensive prognostic and predictive panel for chronic lymphocytic leukemia: a next-generation sequencing tool suitable for clinical practice and study of genetic architecture behind the disease progress
AGATHANGELIDIS, A., A. CHATZIDIMITRIOU, K. GEMENETZI, V. GIUDICELLI, M. KARYPIDOU, Karla PLEVOVÁ, Z. DAVIS, X.J. YAN, S. JEROMIN, C. SCHNEIDER, L.B. PEDERSEN, R.C. TSCHUMPER, L.A. SUTTON, P. BALIAKAS, L. SCARFO, E.J. VAN GASTEL, M. ARMAND, E. TAUSCH, B. BIDERMAN, C. BAER, D. BAGNARA, A. NAVARRO, A.L. DE SEPTENVILLE, V. GUIDO, G. MITTERBAUER-HOHENDANNER, A. DIMOVSKI, C. BRIEGHEL, S. LAWLESS, M. MEGGENDORFER, Kamila STRÁNSKÁ, M. RITGEN, M. FACCO, C. TRESOLDI, A. VISENTIN, A. PATRIARCA, M. CATHERWOOD, L. BONELLO, A. SUDARIKOV, K. VANURA, M. ROUMELIOTI, H.S. FRANCOVA, T. MOYSIADIS, S. VERONESE, K. GIANNOPOULOS, L. MANSOURI, T. KARAN-DJURASEVIC, R. SANDALTZOPOULOS, C. BODOR, F. FAIS, A. KATER, I. PANOVSKA, D. ROSSI, S. ALSHEMMARI, P. PANAGIOTIDIS, P. COSTEAS, B. ESPINET, D. ANTIC, L. FORONI, M. MONTILLO, L. TRENTIN, N. STAVROYIANNI, G. GAIDANO, P.F. DI CELLE, C. NIEMANN, E. CAMPO, A. ANAGNOSTOPOULOS, C. POTT, K. FISCHER, M. HALLEK, D. OSCIER, S. STILGENBAUER, C. HAFERLACH, D. JELINEK, N. CHIORAZZI, Šárka POSPÍŠILOVÁ, M.P. LEFRANC, S. KOSSIDA, A.W. LANGERAK, Cx. BELESSI, F. DAVI, R. ROSENQUIST, P. GHIA a K. STAMATOPOULOS. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. Washington DC, USA: American Society of Hematology, 2021, roč. 137, č. 10, s. 1365-1376. ISSN 0006-4971. Dostupné z: https://dx.doi.org/10.1182/blood.2020007039.
@article{1813390, author = {Agathangelidis, A. and Chatzidimitriou, A. and Gemenetzi, K. and Giudicelli, V. and Karypidou, M. and Plevová, Karla and Davis, Z. and Yan, X.J. and Jeromin, S. and Schneider, C. and Pedersen, L.B. and Tschumper, R.C. and Sutton, L.A. and Baliakas, P. and Scarfo, L. and van Gastel, E.J. and Armand, M. and Tausch, E. and Biderman, B. and Baer, C. and Bagnara, D. and Navarro, A. and de Septenville, A.L. and Guido, V. and MitterbauerandHohendanner, G. and Dimovski, A. and Brieghel, C. and Lawless, S. and Meggendorfer, M. and Stránská, Kamila and Ritgen, M. and Facco, M. and Tresoldi, C. and Visentin, A. and Patriarca, A. and Catherwood, M. and Bonello, L. and Sudarikov, A. and Vanura, K. and Roumelioti, M. and Francova, H.S. and Moysiadis, T. and Veronese, S. and Giannopoulos, K. and Mansouri, L. and KaranandDjurasevic, T. and Sandaltzopoulos, R. and Bodor, C. and Fais, F. and Kater, A. and Panovska, I. and Rossi, D. and Alshemmari, S. and Panagiotidis, P. and Costeas, P. and Espinet, B. and Antic, D. and Foroni, L. and Montillo, M. and Trentin, L. and Stavroyianni, N. and Gaidano, G. and di Celle, P.F. and Niemann, C. and Campo, E. and Anagnostopoulos, A. and Pott, C. and Fischer, K. and Hallek, M. and Oscier, D. and Stilgenbauer, S. and Haferlach, C. and Jelinek, D. and Chiorazzi, N. and Pospíšilová, Šárka and Lefranc, M.P. and Kossida, S. and Langerak, A.W. and Belessi, Cx. and Davi, F. and Rosenquist, R. and Ghia, P. and Stamatopoulos, K.}, article_location = {Washington DC, USA}, article_number = {10}, doi = {http://dx.doi.org/10.1182/blood.2020007039}, keywords = {B lymphocyte receptor; immunoglobulin; immunoglobulin heavy chain; immunoglobulin heavy chain}, language = {eng}, issn = {0006-4971}, journal = {Blood}, title = {Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL}, url = {https://ashpublications.org/blood/article/137/10/1365/463992/Higher-order-connections-between-stereotyped}, volume = {137}, year = {2021} }
TY - JOUR ID - 1813390 AU - Agathangelidis, A. - Chatzidimitriou, A. - Gemenetzi, K. - Giudicelli, V. - Karypidou, M. - Plevová, Karla - Davis, Z. - Yan, X.J. - Jeromin, S. - Schneider, C. - Pedersen, L.B. - Tschumper, R.C. - Sutton, L.A. - 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. - Stránská, Kamila - 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-Djurasevic, T. - Sandaltzopoulos, R. - Bodor, C. - Fais, F. - Kater, A. - Panovska, I. - Rossi, D. - Alshemmari, S. - Panagiotidis, P. - Costeas, P. - Espinet, B. - Antic, 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. - Pospíšilová, Šárka - Lefranc, M.P. - Kossida, S. - Langerak, A.W. - Belessi, Cx. - Davi, F. - Rosenquist, R. - Ghia, P. - Stamatopoulos, K. PY - 2021 TI - Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL JF - Blood VL - 137 IS - 10 SP - 1365-1376 EP - 1365-1376 PB - American Society of Hematology SN - 00064971 KW - B lymphocyte receptor KW - immunoglobulin KW - immunoglobulin heavy chain KW - immunoglobulin heavy chain UR - https://ashpublications.org/blood/article/137/10/1365/463992/Higher-order-connections-between-stereotyped 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. ER -
AGATHANGELIDIS, A., A. CHATZIDIMITRIOU, K. GEMENETZI, V. GIUDICELLI, M. KARYPIDOU, Karla PLEVOVÁ, Z. DAVIS, X.J. YAN, S. JEROMIN, C. SCHNEIDER, L.B. PEDERSEN, R.C. TSCHUMPER, L.A. SUTTON, P. BALIAKAS, L. SCARFO, E.J. VAN GASTEL, M. ARMAND, E. TAUSCH, B. BIDERMAN, C. BAER, D. BAGNARA, A. NAVARRO, A.L. DE SEPTENVILLE, V. GUIDO, G. MITTERBAUER-HOHENDANNER, A. DIMOVSKI, C. BRIEGHEL, S. LAWLESS, M. MEGGENDORFER, Kamila STRÁNSKÁ, M. RITGEN, M. FACCO, C. TRESOLDI, A. VISENTIN, A. PATRIARCA, M. CATHERWOOD, L. BONELLO, A. SUDARIKOV, K. VANURA, M. ROUMELIOTI, H.S. FRANCOVA, T. MOYSIADIS, S. VERONESE, K. GIANNOPOULOS, L. MANSOURI, T. KARAN-DJURASEVIC, R. SANDALTZOPOULOS, C. BODOR, F. FAIS, A. KATER, I. PANOVSKA, D. ROSSI, S. ALSHEMMARI, P. PANAGIOTIDIS, P. COSTEAS, B. ESPINET, D. ANTIC, L. FORONI, M. MONTILLO, L. TRENTIN, N. STAVROYIANNI, G. GAIDANO, P.F. DI CELLE, C. NIEMANN, E. CAMPO, A. ANAGNOSTOPOULOS, C. POTT, K. FISCHER, M. HALLEK, D. OSCIER, S. STILGENBAUER, C. HAFERLACH, D. JELINEK, N. CHIORAZZI, Šárka POSPÍŠILOVÁ, M.P. LEFRANC, S. KOSSIDA, A.W. LANGERAK, Cx. BELESSI, F. DAVI, R. ROSENQUIST, P. GHIA a K. STAMATOPOULOS. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. \textit{Blood}. Washington DC, USA: American Society of Hematology, 2021, roč.~137, č.~10, s.~1365-1376. ISSN~0006-4971. Dostupné z: https://dx.doi.org/10.1182/blood.2020007039.