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

J 2021

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

AGATHANGELIDIS, A.; A. CHATZIDIMITRIOU; K. GEMENETZI; V. GIUDICELLI; M. KARYPIDOU et. al.

Basic information

Original name

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

Authors

AGATHANGELIDIS, A.; A. CHATZIDIMITRIOU; K. GEMENETZI; V. GIUDICELLI; M. KARYPIDOU; Karla PLEVOVÁ (203 Czech Republic, belonging to the institution); 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 Czech Republic, belonging to the institution); 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 Czech Republic, guarantor, belonging to the institution); M.P. LEFRANC; S. KOSSIDA; A.W. LANGERAK; Cx. BELESSI; F. DAVI; R. ROSENQUIST; P. GHIA and K. STAMATOPOULOS

Edition

Blood, Washington DC, USA, American Society of Hematology, 2021, 0006-4971

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 25.669

RIV identification code

RIV/00216224:14740/21:00120185

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.1182/blood.2020007039

UT WoS

000646099500016

EID Scopus

2-s2.0-85102607193

Keywords in English

B lymphocyte receptor; immunoglobulin; immunoglobulin heavy chain; immunoglobulin heavy chain

Abstract

In the original language

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.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

NV19-03-00091, research and development project

Name: 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: Ministry of Health of the CR

Cite

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 and K. STAMATOPOULOS. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. Washington DC, USA: American Society of Hematology, 2021, vol. 137, No 10, p. 1365-1376. ISSN 0006-4971. Available from: https://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 = {https://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 and 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, vol.~137, No~10, p.~1365-1376. ISSN~0006-4971. Available from: https://doi.org/10.1182/blood.2020007039.

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