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Citations to this article

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.
F Fais, … , M Ferrarini, N Chiorazzi
F Fais, … , M Ferrarini, N Chiorazzi
Published October 15, 1998
Citation Information: J Clin Invest. 1998;102(8):1515-1525. https://doi.org/10.1172/JCI3009.
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Research Article Article has an altmetric score of 9

Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.

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Abstract

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the VH genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.

Authors

F Fais, F Ghiotto, S Hashimoto, B Sellars, A Valetto, S L Allen, P Schulman, V P Vinciguerra, K Rai, L Z Rassenti, T J Kipps, G Dighiero, H W Schroeder Jr, M Ferrarini, N Chiorazzi

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1981 Total
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Citations to this article in year 2010 (31)

Title and authors Publication Year
Stereotypical chronic lymphocytic leukemia B-cell receptors recognize survival promoting antigens on stromal cells
M Binder, B Léchenne, R Ummanni, C Scharf, S Balabanov, M Trusch, H Schlüter, I Braren, E Spillner, M Trepel
PloS one 2010
Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors
M Marincevic, M Mansouri, M Kanduri, A Isaksson, H Göransson, KE Smedby, J Jurlander, G Juliusson, F Davi, K Stamatopoulos, R Rosenquist
Haematologica 2010
High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors
M Marincevic, N Cahill, R Gunnarsson, A Isaksson, M Mansouri, H Göransson, M Rasmussen, M Jansson, F Ryan, K Karlsson, HO Adami, F Davi, J Jurlander, G Juliusson, K Stamatopoulos, R Rosenquist
Haematologica 2010
Intraclonal diversification of immunoglobulin light chains in a subset of chronic lymphocytic leukemia alludes to antigen-driven clonal evolution
E Kostareli, LA Sutton, A Hadzidimitriou, N Darzentas, A Kouvatsi, A Tsaftaris, A Anagnostopoulos, R Rosenquist, K Stamatopoulos
Leukemia 2010
Chronic lymphocytic leukaemia: a disease of activated monoclonal B cells
RN Damle, C Calissano, N Chiorazzi
Best Practice & Research Clinical Haematology 2010
Dichotomy in NF-kappaB signaling and chemoresistance in immunoglobulin variable heavy-chain-mutated versus unmutated CLL cells upon CD40/TLR9 triggering
JM Tromp, SH Tonino, JA Elias, A Jaspers, DM Luijks, AP Kater, RA van Lier, MH van Oers, E Eldering
Oncogene 2010
B-cell receptor epitope recognition correlates with the clinical course of chronic lymphocytic leukemia
M Binder, F Müller, A Jackst, B Léchenne, M Pantic, U Bacher, C Eulenburg, H Veelken, R Mertelsmann, R Pasqualini, W Arap, M Trepel
Cancer 2010
Oligoclonality, impaired class switch and B-cell memory responses in WHIM syndrome
PJ Guire, C Cunningham-Rundles, H Ochs, GA Diaz
Clinical Immunology 2010
Single-Agent Lenalidomide in the Treatment of Previously Untreated Chronic Lymphocytic Leukemia
CI Chen, PL Bergsagel, H Paul, W Xu, A Lau, N Dave, V Kukreti, E Wei, C Leung-Hagesteijn, ZH Li, J Brandwein, M Pantoja, J Johnston, S Gibson, T Hernandez, D Spaner, S Trudel
Journal of Clinical Oncology 2010
Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments
M Perez, A Pacchiarotti, M Frontani, E Pescarmona, E Caprini, GA Lombardo, G Russo, T Faraggiana
British Journal of Dermatology 2010
Molecular and clinical features of chronic lymphocytic leukemia with stereotyped B-cell receptors in a Ukrainian cohort
N Bilous, R Bomben, MD Bo, D Capello, F Forconi, L Laurenti, F Bertoni, DG Efremov, R Marasca, GD Poeta, Z Martina, I Kryachouk, I Dyagil, G Gaidano, A Chumak, V Gattei, I Abramenko
Leukemia & Lymphoma 2010
Antigens in chronic lymphocytic leukemia—Implications for cell origin and leukemogenesis
A Rosén, F Murray, C Evaldsson, R Rosenquist
Seminars in Cancer Biology 2010
Immunohistochemical detection of ZAP70 in chronic lymphocytic leukemia predicts immunoglobulin heavy chain gene mutation status and time to progression
JH Admirand, RJ Knoblock, KR Coombes, C Tam, EJ Schlette, WG Wierda, A Ferrajoli, S O'Brien, MJ Keating, R Luthra, LJ Medeiros, LV Abruzzo
Modern Pathology 2010
Polymerase chain reaction (PCR) detection of B cell clonality in Sjögren's syndrome patients: a diagnostic tool of clonal expansion
LM Guzmán, D Castillo, SO Aguilera
Clinical & Experimental Immunology 2010
Immunoglobulin heavy chain V-D-J gene rearrangement and mutational status in Uruguayan patients with chronic lymphocytic leukemia
S Bianchi, P Moreno, AI Landoni, H Naya, P Oppezzo, G Dighiero, R Gabús, O Pritsch
Leukemia & Lymphoma 2010
Activation-induced cytidine deaminase splicing patterns in chronic lymphocytic leukemia
F Marantidou, A Dagklis, E Stalika, P Korkolopoulou, A Saetta, A Anagnostopoulos, N Laoutaris, K Stamatopoulos, C Belessi, Z Scouras, E Patsouris
Blood Cells, Molecules, and Diseases 2010
Chronic lymphocytic leukemia in a Japanese population: varied immunophenotypic profile, distinctive usage of frequently mutatedIGHgene, and indolent clinical behavior
J Tomomatsu, Y Isobe, K Oshimi, Y Tabe, K Ishii, M Noguchi, T Hirano, N Komatsu, K Sugimoto
Leukemia & Lymphoma 2010
Telomere/telomerase interplay in virus-driven and virus-independent lymphomagenesis: Pathogenic and clinical implications
R Dolcetti, AD Rossi
Medicinal Research Reviews 2010
Genetic variation and risk of chronic lymphocytic leukaemia
D Crowther-Swanepoel, RS Houlston
Seminars in Cancer Biology 2010
New insights into the pathogenesis of chronic lymphocytic leukemia
U Klein, R Dalla-Favera
Seminars in Cancer Biology 2010
Moving from prognostic to predictive factors in chronic lymphocytic leukaemia (CLL)
T Zenz, S Fröhling, D Mertens, H Döhner, S Stilgenbauer
Best Practice & Research Clinical Haematology 2010
The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy
CD Schweighofer, YO Huh, R Luthra, RL Sargent, RP Ketterling, RA Knudson, LL Barron, LJ Medeiros, MJ Keating, LV Abruzzo
International Journal of Cancer 2010
Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia
L Weiss, T Melchardt, A Egle, C Grabmer, R Greil, I Tinhofer
Cancer 2010
Novel Insights into the Biology of CLL
MC Lanasa
Hematology 2010
Biologic and clinical significance of molecular profiling in Chronic Lymphocytic Leukemia
T Butler, JG Gribben
Blood Reviews 2010
NF-κB as a therapeutic target in chronic lymphocytic leukemia
M Lopez-Guerra, D Colomer
Expert Opinion on Therapeutic Targets 2010
Stereotypical Chronic Lymphocytic Leukemia B-Cell Receptors Recognize Survival Promoting Antigens on Stromal Cells
M Binder, B Léchenne, R Ummanni, C Scharf, S Balabanov, M Trusch, H Schlüter, I Braren, E Spillner, M Trepel, D Gullberg
PloS one 2010
MicroRNAs in Cancer Translational Research
WC Cho
2010
Molecular Pathology of Hematolymphoid Diseases
CH Dunphy
2010
Cancer Management in Man: Chemotherapy, Biological Therapy, Hyperthermia and Supporting Measures
BR Minev
2010
Mechanisms of Oncogenesis
D Coppola
2010

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