Stereotyped B-cell receptors in one-third of chronic
lymphocytic leukemia: a molecular classification with
implications for targeted therapies

J 2012

Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies

AGATHANGELIDIS, A., Nikos DARZENTAS, A. HADZIDIMITRIOU, X. BROCHET, F. MURRAY et. al.

Basic information

Original name

Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies

Name in Czech

Stereotypní B-buněčných receptorů v jedné třetině chronickou lymfocytární leukemií: molekulární klasifikace s důsledky pro cílených terapií

Authors

AGATHANGELIDIS, A. (300 Greece), Nikos DARZENTAS (300 Greece), A. HADZIDIMITRIOU (300 Greece), X. BROCHET (250 France), F. MURRAY (752 Sweden), X. YAN (840 United States of America), Z. DAVIS (826 United Kingdom of Great Britain and Northern Ireland), E. VAN GASTEL-MOL (528 Netherlands), C. TRESOLDI (380 Italy), Ch. CHU (840 United States of America), N. CAHILL (752 Sweden), V. GIUDICELLI (300 Greece), Boris TICHÝ (203 Czech Republic, belonging to the institution), L. PEDERSEN (208 Denmark), L. FORONI (826 United Kingdom of Great Britain and Northern Ireland), L. BONELLO (380 Italy), A. JANUS (380 Italy), K. SMEDBY (752 Sweden), A. ANAGNOSTOPOULOS (300 Greece), H. MERLE-BERAL (250 France), N. LAOUTARIS (300 Greece), G. JULIUSSON (752 Sweden), P. DI CELLE (380 Italy), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), J. JURLANDER (208 Denmark), Ch. GEISLER (208 Denmark), A. TSAFTARIS (300 Greece), M. LEFRANC (250 France), A. LANGERAK (528 Netherlands), D. OSCIER (826 United Kingdom of Great Britain and Northern Ireland), N. CHIORAZZI (840 United States of America), Ch. BELESSI (300 Greece), F. DAVI (250 France), R. ROSENQUIST (752 Sweden), P. GHIA (380 Italy, guarantor) and K. STAMATOPOULOS (300 Greece)

Edition

Blood, Washington, DC, American Society of Hematology, 2012, 0006-4971

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 9.060

RIV identification code

RIV/00216224:14740/12:00062998

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1182/blood-2011-11-393694

UT WoS

000305286900021

Keywords in English

HEAVY-CHAIN IIA; ANTIGEN RECEPTORS; APOPTOTIC CELLS; IMMUNOGLOBULIN; ANTIBODIES; IG; GENES; REPERTOIRE; SELECTION; SEQUENCE

Abstract

V originále

Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1:2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR stereotypy in other B-cell malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each, collectively accounting for 943 sequences or one-eighth of the cohort. Hence, this compartmentalized examination of VH sequences may pave the way toward a molecular classification of CLL with implications for targeted therapeutic interventions, applicable to a significant number of patients assigned to the same subset.

Citovat

AGATHANGELIDIS, A., Nikos DARZENTAS, A. HADZIDIMITRIOU, X. BROCHET, F. MURRAY, X. YAN, Z. DAVIS, E. VAN GASTEL-MOL, C. TRESOLDI, Ch. CHU, N. CAHILL, V. GIUDICELLI, Boris TICHÝ, L. PEDERSEN, L. FORONI, L. BONELLO, A. JANUS, K. SMEDBY, A. ANAGNOSTOPOULOS, H. MERLE-BERAL, N. LAOUTARIS, G. JULIUSSON, P. DI CELLE, Šárka POSPÍŠILOVÁ, J. JURLANDER, Ch. GEISLER, A. TSAFTARIS, M. LEFRANC, A. LANGERAK, D. OSCIER, N. CHIORAZZI, Ch. BELESSI, F. DAVI, R. ROSENQUIST, P. GHIA and K. STAMATOPOULOS. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood. Washington, DC: American Society of Hematology, 2012, vol. 119, No 19, p. 4467-4475. ISSN 0006-4971. Available from: https://dx.doi.org/10.1182/blood-2011-11-393694.

@article{1082989,
   author = {Agathangelidis, A. and Darzentas, Nikos and Hadzidimitriou, A. and Brochet, X. and Murray, F. and Yan, X. and Davis, Z. and van GastelandMol, E. and Tresoldi, C. and Chu, Ch. and Cahill, N. and Giudicelli, V. and Tichý, Boris and Pedersen, L. and Foroni, L. and Bonello, L. and Janus, A. and Smedby, K. and Anagnostopoulos, A. and MerleandBeral, H. and Laoutaris, N. and Juliusson, G. and di Celle, P. and Pospíšilová, Šárka and Jurlander, J. and Geisler, Ch. and Tsaftaris, A. and Lefranc, M. and Langerak, A. and Oscier, D. and Chiorazzi, N. and Belessi, Ch. and Davi, F. and Rosenquist, R. and Ghia, P. and Stamatopoulos, K.},
   article_location = {Washington, DC},
   article_number = {19},
   doi = {http://dx.doi.org/10.1182/blood-2011-11-393694},
   keywords = {HEAVY-CHAIN IIA; ANTIGEN RECEPTORS; APOPTOTIC CELLS; IMMUNOGLOBULIN; ANTIBODIES; IG; GENES; REPERTOIRE; SELECTION; SEQUENCE},
   language = {eng},
   issn = {0006-4971},
   journal = {Blood},
   title = {Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies},
   volume = {119},
   year = {2012}
}

TY  - JOUR
ID  - 1082989
AU  - Agathangelidis, A. - Darzentas, Nikos - Hadzidimitriou, A. - Brochet, X. - Murray, F. - Yan, X. - Davis, Z. - van Gastel-Mol, E. - Tresoldi, C. - Chu, Ch. - Cahill, N. - Giudicelli, V. - Tichý, Boris - Pedersen, L. - Foroni, L. - Bonello, L. - Janus, A. - Smedby, K. - Anagnostopoulos, A. - Merle-Beral, H. - Laoutaris, N. - Juliusson, G. - di Celle, P. - Pospíšilová, Šárka - Jurlander, J. - Geisler, Ch. - Tsaftaris, A. - Lefranc, M. - Langerak, A. - Oscier, D. - Chiorazzi, N. - Belessi, Ch. - Davi, F. - Rosenquist, R. - Ghia, P. - Stamatopoulos, K.
PY  - 2012
TI  - Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies
JF  - Blood
VL  - 119
IS  - 19
SP  - 4467-4475
EP  - 4467-4475
PB  - American Society of Hematology
SN  - 00064971
KW  - HEAVY-CHAIN IIA
KW  - ANTIGEN RECEPTORS
KW  - APOPTOTIC CELLS
KW  - IMMUNOGLOBULIN
KW  - ANTIBODIES
KW  - IG
KW  - GENES
KW  - REPERTOIRE
KW  - SELECTION
KW  - SEQUENCE
N2  - Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as well as the identification of "CLL-biased" features in BCR Ig stereotypes. To this end, we examined 7596 Ig VH (IGHV-IGHD-IGHJ) sequences from 7424 CLL patients, 3 times the size of the largest published series, with an updated version of our purpose-built clustering algorithm. We document that CLL may be subdivided into 2 distinct categories: one with stereotyped and the other with nonstereotyped BCRs, at an approximate ratio of 1:2, and provide evidence suggesting a different ontogeny for these 2 categories. We also show that subset-defining sequence patterns in CLL differ from those underlying BCR stereotypy in other B-cell malignancies. Notably, 19 major subsets contained from 20 to 213 sequences each, collectively accounting for 943 sequences or one-eighth of the cohort. Hence, this compartmentalized examination of VH sequences may pave the way toward a molecular classification of CLL with implications for targeted therapeutic interventions, applicable to a significant number of patients assigned to the same subset.
ER  -

AGATHANGELIDIS, A., Nikos DARZENTAS, A. HADZIDIMITRIOU, X. BROCHET, F. MURRAY, X. YAN, Z. DAVIS, E. VAN GASTEL-MOL, C. TRESOLDI, Ch. CHU, N. CAHILL, V. GIUDICELLI, Boris TICHÝ, L. PEDERSEN, L. FORONI, L. BONELLO, A. JANUS, K. SMEDBY, A. ANAGNOSTOPOULOS, H. MERLE-BERAL, N. LAOUTARIS, G. JULIUSSON, P. DI CELLE, Šárka POSPÍŠILOVÁ, J. JURLANDER, Ch. GEISLER, A. TSAFTARIS, M. LEFRANC, A. LANGERAK, D. OSCIER, N. CHIORAZZI, Ch. BELESSI, F. DAVI, R. ROSENQUIST, P. GHIA and K. STAMATOPOULOS. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. \textit{Blood}. Washington, DC: American Society of Hematology, 2012, vol.~119, No~19, p.~4467-4475. ISSN~0006-4971. Available from: https://dx.doi.org/10.1182/blood-2011-11-393694.

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