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Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia

BACKGROUND: Chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis (MBL) with (MBL(hi)) or without (MBL(lo)) absolute B-lymphocytosis precedes most CLL cases,the specific determinants for malignant progression remaining unknown. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, simultane...

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Autores principales: Henriques, Ana, Rodríguez-Caballero, Arancha, Nieto, Wendy G., Langerak, Anton W., Criado, Ignacio, Lécrevisse, Quentin, González, Marcos, Pais, Maria L., Paiva, Artur, Almeida, Julia, Orfao, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701012/
https://www.ncbi.nlm.nih.gov/pubmed/23844084
http://dx.doi.org/10.1371/journal.pone.0067751
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author Henriques, Ana
Rodríguez-Caballero, Arancha
Nieto, Wendy G.
Langerak, Anton W.
Criado, Ignacio
Lécrevisse, Quentin
González, Marcos
Pais, Maria L.
Paiva, Artur
Almeida, Julia
Orfao, Alberto
author_facet Henriques, Ana
Rodríguez-Caballero, Arancha
Nieto, Wendy G.
Langerak, Anton W.
Criado, Ignacio
Lécrevisse, Quentin
González, Marcos
Pais, Maria L.
Paiva, Artur
Almeida, Julia
Orfao, Alberto
author_sort Henriques, Ana
collection PubMed
description BACKGROUND: Chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis (MBL) with (MBL(hi)) or without (MBL(lo)) absolute B-lymphocytosis precedes most CLL cases,the specific determinants for malignant progression remaining unknown. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, simultaneous iFISH and molecular analysis of well-established cytogenetic alterations of chromosomes 11, 12, 13, 14 and 17 together with the pattern of rearrangement of the IGHV genes were performed in CLL-like cells from MBL and CLL cases. Our results based on 78 CLL-like MBL and 117 CLL clones from 166 subjects living in the same geographical area, show the existence of three major groups of clones with distinct but partially overlapping patterns of IGHV gene usage, IGHV mutational status and cytogenetic alterations. These included a group enriched in MBL(lo) clones expressing specific IGHV subgroups (e.g. VH3-23) with no or isolated good-prognosis cytogenetic alterations, a second group which mainly consisted of clinical MBL(hi) and advanced stage CLL with a skewed but different CLL-associated IGHV gene repertoire (e.g. VH1-69), frequently associated with complex karyotypes and poor-prognosis cytogenetic alterations, and a third group of clones with intermediate features, with prevalence of mutated IGHV genes, and higher numbers of del(13q)(+) clonal B-cells. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the specific IGHV repertoire and IGHV mutational status of CLL-like B-cell clones may modulate the type of cytogenetic alterations acquired, their rate of acquisition and/or potentially also their clinical consequences. Further long-term follow-up studies investigating the IGHV gene repertoire of MBL(lo) clones in distinct geographic areas and microenvironments are required to confirm our findings and shed light on the potential role of some antigen-binding BCR specificities contributing to clonal evolution.
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spelling pubmed-37010122013-07-10 Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia Henriques, Ana Rodríguez-Caballero, Arancha Nieto, Wendy G. Langerak, Anton W. Criado, Ignacio Lécrevisse, Quentin González, Marcos Pais, Maria L. Paiva, Artur Almeida, Julia Orfao, Alberto PLoS One Research Article BACKGROUND: Chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis (MBL) with (MBL(hi)) or without (MBL(lo)) absolute B-lymphocytosis precedes most CLL cases,the specific determinants for malignant progression remaining unknown. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, simultaneous iFISH and molecular analysis of well-established cytogenetic alterations of chromosomes 11, 12, 13, 14 and 17 together with the pattern of rearrangement of the IGHV genes were performed in CLL-like cells from MBL and CLL cases. Our results based on 78 CLL-like MBL and 117 CLL clones from 166 subjects living in the same geographical area, show the existence of three major groups of clones with distinct but partially overlapping patterns of IGHV gene usage, IGHV mutational status and cytogenetic alterations. These included a group enriched in MBL(lo) clones expressing specific IGHV subgroups (e.g. VH3-23) with no or isolated good-prognosis cytogenetic alterations, a second group which mainly consisted of clinical MBL(hi) and advanced stage CLL with a skewed but different CLL-associated IGHV gene repertoire (e.g. VH1-69), frequently associated with complex karyotypes and poor-prognosis cytogenetic alterations, and a third group of clones with intermediate features, with prevalence of mutated IGHV genes, and higher numbers of del(13q)(+) clonal B-cells. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the specific IGHV repertoire and IGHV mutational status of CLL-like B-cell clones may modulate the type of cytogenetic alterations acquired, their rate of acquisition and/or potentially also their clinical consequences. Further long-term follow-up studies investigating the IGHV gene repertoire of MBL(lo) clones in distinct geographic areas and microenvironments are required to confirm our findings and shed light on the potential role of some antigen-binding BCR specificities contributing to clonal evolution. Public Library of Science 2013-07-03 /pmc/articles/PMC3701012/ /pubmed/23844084 http://dx.doi.org/10.1371/journal.pone.0067751 Text en © 2013 Henriques et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Henriques, Ana
Rodríguez-Caballero, Arancha
Nieto, Wendy G.
Langerak, Anton W.
Criado, Ignacio
Lécrevisse, Quentin
González, Marcos
Pais, Maria L.
Paiva, Artur
Almeida, Julia
Orfao, Alberto
Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia
title Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia
title_full Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia
title_fullStr Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia
title_full_unstemmed Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia
title_short Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia
title_sort combined patterns of ighv repertoire and cytogenetic/molecular alterations in monoclonal b lymphocytosis versus chronic lymphocytic leukemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701012/
https://www.ncbi.nlm.nih.gov/pubmed/23844084
http://dx.doi.org/10.1371/journal.pone.0067751
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