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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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Total citations by year

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
Citations: 2 7 9 10 28 16 11 17 25 18 27 25 48 29 37 31 33 30 36 37 33 35 32 29 30 26 12 1 674
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Citations to this article in year 2012 (29)

Title and authors Publication Year
IGHV-unmutated and IGHV-mutated chronic lymphocytic leukemia cells produce activation-induced deaminase protein with a full range of biologic functions
PE Patten, CC Chu, E Albesiano, RN Damle, XJ Yan, D Kim, L Zhang, AR Magli, J Barrientos, JE Kolitz, SL Allen, KR Rai, S Roa, PK Mongini, T MacCarthy, MD Scharff, N Chiorazzi
Blood 2012
Quantitative DNA methylation analysis identifies a single CpG dinucleotide important for ZAP-70 expression and predictive of prognosis in chronic lymphocytic leukemia
R Claus, DM Lucas, S Stilgenbauer, AS Ruppert, L Yu, M Zucknick, D Mertens, A Bühler, CC Oakes, RA Larson, NE Kay, DF Jelinek, TJ Kipps, LZ Rassenti, JG Gribben, H Döhner, NA Heerema, G Marcucci, C Plass, JC Byrd
Journal of Clinical Oncology 2012
Pathogenesis of Human B Cell Lymphomas
AL Shaffer, RM Young, LM Staudt
Annual Review of Immunology 2012
Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies
A Agathangelidis, N Darzentas, A Hadzidimitriou, X Brochet, F Murray, XJ Yan, Z Davis, EJ van Gastel-Mol, C Tresoldi, CC Chu, N Cahill, V Giudicelli, B Tichy, LB Pedersen, L Foroni, L Bonello, A Janus, K Smedby, A Anagnostopoulos, H Merle-Beral, N Laoutaris, G Juliusson, PF di Celle, S Pospisilova, J Jurlander, C Geisler, A Tsaftaris, MP Lefranc, AW Langerak, DG Oscier, N Chiorazzi, C Belessi, F Davi, R Rosenquist, P Ghia, K Stamatopoulos
Blood 2012
Immunoglobulin gene repertoire in chronic lymphocytic leukemia: insight into antigen selection and microenvironmental interactions
E Kostareli, M Gounari, A Agathangelidis, K Stamatopoulos
Mediterranean journal of hematology and infectious diseases 2012
Distinct innate immunity pathways to activation and tolerance in subgroups of chronic lymphocytic leukemia with distinct immunoglobulin receptors
S Ntoufa, A Vardi, N Papakonstantinou, A Anagnostopoulos, V Aleporou-Marinou, C Belessi, P Ghia, F Caligaris-Cappio, M Muzio, K Stamatopoulos
Molecular Medicine 2012
Lymphoma
R Küppers
Lymphoma 2012
Lymphoma
R Küppers
Lymphoma 2012
Lymphoma
R Küppers
Lymphoma 2012
T-cell independent, B-cell receptor-mediated induction of telomerase activity differs among IGHV mutation-based subgroups of chronic lymphocytic leukemia patients
RN Damle, S Temburni, T Banapour, S Paul, PK Mongini, SL Allen, JE Kolitz, KR Rai, N Chiorazzi
Blood 2012
Stromal endothelial cells establish a bidirectional crosstalk with chronic lymphocytic leukemia cells through the TNF-related factors BAFF, APRIL, and CD40L
M Cols, CM Barra, B He, I Puga, W Xu, A Chiu, W Tam, DM Knowles, SR Dillon, JP Leonard, RR Furman, K Chen, A Cerutti
Journal of immunology (Baltimore, Md. : 1950) 2012
Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes
S Ferrero, D Capello, M Svaldi, M Boi, D Gatti, D Drandi, D Rossi, S Barbiero, B Mantoan, E Mantella, M Zanni, P Ghione, A Larocca, R Passera, F Bertoni, V Gattei, F Forconi, L Laurenti, GD Poeta, R Marasca, S Cortelazzo, G Gaidano, A Palumbo, M Boccadoro, M Ladetto
Haematologica 2012
Association of Interleukin-6 and Interleukin-8 with Poor Prognosis in Elderly Chronic Lymphocytic Leukemia Patients
JY Yoon, S Lafarge, D Dawe, S Lakhi, R Kumar, C Morales, A Marshall, SB Gibson, JB Johnston
Leukemia and Lymphoma 2012
Through a glass less darkly: apoptosis and the germinal center response to antigen : Apoptosis and the GC response to antigen
V Peperzak, IB Vikstrom, DM Tarlinton
Immunological Reviews 2012
Signaling pathways activated by the B-cell receptor in chronic lymphocytic leukemia
MT Scupoli, G Pizzolo
Expert Review of Hematology 2012
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RC Tschumper, YW Asmann, A Hossain, PM Huddleston, X Wu, A Dispenzieri, BW Eckloff, DF Jelinek
Oncotarget 2012
Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia
T Karan-Djurasevic, V Palibrk, T Kostic, V Spasovski, G Nikcevic, S Srzentic, M Colovic, N Colovic, A Vidovic, D Antic, B Mihaljevic, S Pavlovic, N Tosic
Clinical Lymphoma Myeloma and Leukemia 2012
Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression
HY Chuang, L Rassenti, M Salcedo, K Licon, A Kohlmann, T Haferlach, R Foa, T Ideker, TJ Kipps
Blood 2012
Chromosome 2p gain in monoclonal B-cell lymphocytosis and in early stage chronic lymphocytic leukemia
S Fabris, L Mosca, G Cutrona, M Lionetti, L Agnelli, G Ciceri, M Barbieri, F Maura, S Matis, M Colombo, M Gentile, AG Recchia, EA Pesce, FD Raimondo, C Musolino, M Gobbi, ND Renzo, FR Mauro, M Brugiatelli, F Ilariucci, MG Lipari, F Angrilli, U Consoli, A Fragasso, S Molica, G Festini, I Vincelli, A Cortelezzi, M Federico, F Morabito, M Ferrarini, A Neri
American Journal of Hematology 2012
B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia
F Maura, C Visco, E Falisi, G Reda, S Fabris, L Agnelli, G Tuana, M Lionetti, N Guercini, E Novella, I Nichele, A Montaldi, F Autore, A Gregorini, W Barcellini, V Callea, FR Mauro, L Laurenti, R Foà, A Neri, F Rodeghiero, A Cortelezzi
American Journal of Hematology 2012
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R Ruchlemer, A Polliack
Leukemia & Lymphoma 2012
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LQ Wang, R Liang, CS Chim
Expert Review of Molecular Diagnostics 2012
Immunoglobulin gamma heavy chain gene with somatic hypermutation is frequently expressed in acute myeloid leukemia
X Qiu, X Sun, Z He, J Huang, F Hu, L Chen, P Lin, MJ You, LJ Medeiros, CC Yin
Leukemia 2012
External validation on a prospective basis of a nomogram for predicting the time to first treatment in patients with chronic lymphocytic leukemia
S Molica, D Giannarelli, M Gentile, G Cutrona, ND Renzo, FD Raimondo, A Neri, M Federico, M Ferrrarini, F Morabito
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Blood 2012
Hematologic Cancers: From Molecular Pathobiology to Targeted Therapeutics
J Tao, E Sotomayor
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Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program 2012
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