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Статья
Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL
A. Agathangelidis,
A. Chatzidimitriou,
K. Gemenetzi,
V. Giudicelli,
M. Karypidou,
K. Plevova,
Z. Davis,
X. Yan,
S. Jeromin,
C. Schneider,
L. Pedersen,
R. Tschumper,
L. Sutton,
P. Baliakas,
L. Scarfò,
E. van Gastel,
M. Armand,
E. Tausch,
B. Biderman,
C. Baer,
D. Bagnara,
A. Navarro,
A. Langlois de Septenville,
V. Guido,
G. Mitterbauer-Hohendanner,
A. Dimovski,
C. Brieghel,
S. Lawless,
M. Meggendorfer,
K. Brazdilova,
M. Ritgen,
M. Facco,
C. Tresoldi,
A. Visentin,
A. Patriarca,
M. Catherwood,
L. Bonello,
A. Sudarikov,
K. Vanura,
M. Roumelioti,
H. Skuhrova Francova,
T. Moysiadis,
S. Veronese,
K. Giannopoulos,
L. Mansouri,
T. Karan-Djurasevic,
R. Sandaltzopoulos,
C. Bödör,
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. Francia di Celle,
C. Niemann,
E. Campo,
A. Anagnostopoulos,
C. Pott,
K. Fischer,
M. Hallek,
D. Oscier,
S. Stilgenbauer,
C. Haferlach,
D. Jelinek,
N. Chiorazzi,
S. Pospisilova,
M. Lefranc,
S. Kossida,
A. Langerak,
C. Belessi,
F. Davi,
R. Rosenquist,
P. Ghia,
K. Stamatopoulos,
2021
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. Key Points: • In a series of 29 856 CLL patients, the incidence of BcR stereotypy peaked at 41%. • Higher-order relations exist between stereotyped subsets, particularly for those from U-CLL, for which satellite subsets were identified.
Цитирование
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Версии
- 1. Version of Record от 2021-03-11
Метаданные
Об авторах
-
A. Agathangelidis
Center For Research And Technology - Hellas -
A. Chatzidimitriou
Center For Research And Technology - Hellas, Karolinska Institutet -
K. Gemenetzi
Center For Research And Technology - Hellas, Democritus University of Thrace -
V. Giudicelli
Université de Montpellier -
M. Karypidou
Center For Research And Technology - Hellas -
K. Plevova
Fakultni Nemocnice Brno, Masarykova Univerzita -
Z. Davis
Royal Bournemouth Hospital -
X. Yan
Feinstein Institute for Medical Research -
S. Jeromin
MLL Münchner Leukämielabor GmbH -
C. Schneider
Universitätsklinikum Ulm -
L. Pedersen
Rigshospitalet -
R. Tschumper
Mayo Clinic -
L. Sutton
Karolinska Institutet -
P. Baliakas
Uppsala Universitet -
L. Scarfò
Università Vita-Salute San Raffaele -
E. van Gastel
Erasmus MC -
M. Armand
Sorbonne Universite -
E. Tausch
Universität Ulm -
B. Biderman
National Research Center for Hematology -
C. Baer
MLL Münchner Leukämielabor GmbH -
D. Bagnara
Università degli Studi di Genova -
A. Navarro
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS -
A. Langlois de Septenville
Sorbonne Universite -
V. Guido
Ospedale Niguarda, Milan -
G. Mitterbauer-Hohendanner
Medizinische Universitat Wien -
A. Dimovski
SS Cyril and Methodius University -
C. Brieghel
Rigshospitalet -
S. Lawless
Belfast City Hospital -
M. Meggendorfer
MLL Münchner Leukämielabor GmbH -
K. Brazdilova
Fakultni Nemocnice Brno, Masarykova Univerzita -
M. Ritgen
Universitätsklinikum Schleswig-Holstein Campus Kiel -
M. Facco
Università degli Studi di Padova, Veneto Institute of Molecular Medicine -
C. Tresoldi
IRCCS San Raffaele Scientific Institute -
A. Visentin
Università degli Studi di Padova, Veneto Institute of Molecular Medicine -
A. Patriarca
Università degli Studi del Piemonte Orientale "Amedeo Avogadro" -
M. Catherwood
Belfast City Hospital -
L. Bonello
General Anatomopathology and Molecular Oncogenetics -
A. Sudarikov
National Research Center for Hematology -
K. Vanura
Medizinische Universitat Wien -
M. Roumelioti
National and Kapodistrian University of Athens -
H. Skuhrova Francova
Fakultni Nemocnice Brno -
T. Moysiadis
Center For Research And Technology - Hellas -
S. Veronese
Ospedale Niguarda, Milan -
K. Giannopoulos
Medical University of Lublin -
L. Mansouri
Karolinska Institutet -
T. Karan-Djurasevic
University of Belgrade -
R. Sandaltzopoulos
Democritus University of Thrace -
C. Bödör
Semmelweis Egyetem -
F. Fais
Università degli Studi di Genova, Ospedale Policlinico San Martino -
A. Kater
Universiteit van Amsterdam -
I. Panovska
SS Cyril and Methodius University -
D. Rossi
Oncology Institute of Southern Switzerland -
S. Alshemmari
Kuwait University -
P. Panagiotidis
National and Kapodistrian University of Athens -
P. Costeas
The Center for the Study of Haematological Malignancies, Karaiskakio Foundation -
B. Espinet
Hospital del Mar -
D. Antic
Klinicki Centar Srbije -
L. Foroni
Hammersmith Hospital -
M. Montillo
Ospedale Niguarda, Milan -
L. Trentin
Università degli Studi di Padova, Veneto Institute of Molecular Medicine -
N. Stavroyianni
George Papanicolaou General Hospital -
G. Gaidano
Università degli Studi del Piemonte Orientale "Amedeo Avogadro" -
P. Francia di Celle
General Anatomopathology and Molecular Oncogenetics -
C. Niemann
Rigshospitalet -
E. Campo
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS, Universitat de Barcelona -
A. Anagnostopoulos
Hammersmith Hospital -
C. Pott
Universitätsklinikum Schleswig-Holstein Campus Kiel -
K. Fischer
Uniklinik Köln -
M. Hallek
University of Cologne -
D. Oscier
Royal Bournemouth Hospital -
S. Stilgenbauer
Universität Ulm -
C. Haferlach
MLL Münchner Leukämielabor GmbH -
D. Jelinek
Mayo Clinic Scottsdale-Phoenix, Arizona -
N. Chiorazzi
Feinstein Institute for Medical Research -
S. Pospisilova
Fakultni Nemocnice Brno, Masarykova Univerzita -
M. Lefranc
Université de Montpellier -
S. Kossida
Université de Montpellier -
A. Langerak
Erasmus MC -
C. Belessi
Nikea General Hospital, Athens -
F. Davi
Erasmus MC -
R. Rosenquist
Karolinska Institutet, Karolinska University Hospital -
P. Ghia
Università Vita-Salute San Raffaele -
K. Stamatopoulos
Center For Research And Technology - Hellas, Karolinska Institutet
Название журнала
- Blood
Том
- 137
Выпуск
- 10
Страницы
- 1365-1376
Финансирующая организация
- Bayer
Номер гранта
- 794075
Тип документа
- journal article
Тип лицензии Creative Commons
- CC BY
Правовой статус документа
- Свободная лицензия
Источник
- scopus
