B-Lymphocytes
/ immunology
Cohort Studies
Complementarity Determining Regions
/ genetics
Genetic Predisposition to Disease
Humans
Immunoglobulin Heavy Chains
/ genetics
Immunoglobulin lambda-Chains
/ genetics
Leukemia, Lymphocytic, Chronic, B-Cell
/ genetics
Point Mutation
Receptors, Antigen, B-Cell
/ genetics
B cell antigen receptor (BCR)
autonomous BCR signaling
chronic lymphocytic leukemia (CLL)
immunoglobulin allele IGLV3-21*01
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
25 02 2020
25 02 2020
Historique:
pubmed:
13
2
2020
medline:
18
7
2020
entrez:
13
2
2020
Statut:
ppublish
Résumé
The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementarity-determining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21-derived heavy chains (HCs) with IGLV3-21-derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21
Identifiants
pubmed: 32047037
pii: 1913810117
doi: 10.1073/pnas.1913810117
pmc: PMC7049113
doi:
Substances chimiques
Complementarity Determining Regions
0
Immunoglobulin Heavy Chains
0
Immunoglobulin lambda-Chains
0
Receptors, Antigen, B-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4320-4327Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: H.J. is a cofounder of AVA LifeScience GmbH that has filed patents on antibodies recognizing structures involved in autonomous BCR signaling.
Références
Blood. 2005 Nov 15;106(10):3575-83
pubmed: 16076869
Blood. 2014 Jul 3;124(1):49-62
pubmed: 24797299
Methods Mol Biol. 2019;1989:93-108
pubmed: 31077101
Am J Hematol. 2015 May;90(5):446-60
pubmed: 25908509
Nat Med. 2015 Oct;21(10):1190-8
pubmed: 26366712
Methods Mol Biol. 2012;882:569-604
pubmed: 22665256
Cell Rep. 2017 Dec 12;21(11):3243-3255
pubmed: 29241550
Blood. 2002 Aug 15;100(4):1410-6
pubmed: 12149225
Blood. 2008 May 15;111(10):4916-21
pubmed: 18309034
Blood. 2007 Nov 1;110(9):3352-9
pubmed: 17684154
Nature. 2011 Mar 10;471(7337):189-95
pubmed: 21390126
BMC Bioinformatics. 2016 Feb 04;17:67
pubmed: 26847109
Br J Haematol. 2017 Sep;178(6):983-986
pubmed: 27301611
N Engl J Med. 2004 Aug 26;351(9):893-901
pubmed: 15329427
Blood. 2008 Feb 1;111(3):1524-33
pubmed: 17959859
Nature. 2012 Sep 13;489(7415):309-12
pubmed: 22885698
J Clin Oncol. 2017 Jan 10;35(2):166-174
pubmed: 27870563
Clin Cancer Res. 2018 Oct 15;24(20):5048-5057
pubmed: 29945996
Blood. 1999 Sep 15;94(6):1840-7
pubmed: 10477712
Blood. 2012 Dec 6;120(24):4802-11
pubmed: 23071276
Leuk Lymphoma. 2018 Jul;59(7):1614-1623
pubmed: 29063805
Leukemia. 2017 Feb;31(2):282-291
pubmed: 27811850
Nat Immunol. 2015 May;16(5):534-43
pubmed: 25848865
Nat Commun. 2017 Jun 09;8:15746
pubmed: 28598442
Blood. 2012 May 10;119(19):4467-75
pubmed: 22415752
J Immunol. 2019 Mar 1;202(5):1417-1427
pubmed: 30683703
Cancer Sci. 2009 Apr;100(4):671-7
pubmed: 19220298
Immunity. 2008 Dec 19;29(6):912-21
pubmed: 19084434
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
pubmed: 12434020
J Immunol. 2015 Feb 15;194(4):2022-31
pubmed: 25609839
Eur J Immunol. 2015 Sep;45(9):2698-700
pubmed: 26138551
Blood. 2013 Feb 21;121(8):1403-12
pubmed: 23243274
Clin Cancer Res. 2011 Nov 1;17(21):6778-90
pubmed: 21890456
Immunity. 2007 Mar;26(3):323-33
pubmed: 17331747
Nature. 2015 Oct 22;526(7574):519-24
pubmed: 26200345
Lancet Oncol. 2016 Jun;17(6):779-790
pubmed: 27185642
Lancet Haematol. 2014 Nov;1(2):e74-84
pubmed: 27030157
Blood. 2007 Jan 1;109(1):259-70
pubmed: 16985177
Blood. 1999 Sep 15;94(6):1848-54
pubmed: 10477713