Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment

Autores
Moreno, P.; Abreu, C.; Borge, Mercedes; Palacios, F.; Morande, Pablo Elías; Pegazzano, M.; Bianchi, S.; Landoni, A.I.; Agrelo, R.; Giordano, Mirta Nilda; Dighiero, G.; Gamberale, Romina; Oppezzo, P.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have previously demonstrated that lipoprotein lipase (LPL) is associated to an unmutated immunoglobulin profile and clinical poor outcome in Chronic Lymphocytic Leukemia (CLL). Despite the usefulness of LPL for CLL prognosis, its functional role and the molecular mechanism regulating its expression remain elusive. Since interaction of CLL B-cells with tissue microenvironment favors disease progression by promoting malignant B-cell growth and considering that tissue methylation can be altered by environmental factors, we investigated the methylation status of LPL gene and the possibility that its over-expression could be associated to microenvironment signals. By comparing methylation changes in the LPL-CpG island between unmutated and mutated CLL patients, we could demonstrate a clear association between LPL expression and a demethylation process in the CpG island near the promoter region of the LPL gene. This process can be induced by proliferative and specific stimuli,particularly we found that CLL B-cell activation through the CD40 plus IL-4 pathway led to LPL expression and gene demethylation in LPL negative CLL samples. Overall, these results suggest that an epigenetic mechanism, triggered by the microenvironment, regulates LPL expression in CLL cells.
Fil: Moreno, P.. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Abreu, C.. Instituto Pasteur de Montevideo; Uruguay
Fil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Palacios, F.. Instituto Pasteur de Montevideo; Uruguay
Fil: Morande, Pablo Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Pegazzano, M.. Instituto Pasteur de Montevideo; Uruguay
Fil: Bianchi, S.. Instituto Pasteur de Montevideo; Uruguay
Fil: Landoni, A.I.. Hospital Maciel; Uruguay
Fil: Agrelo, R.. Instituto Pasteur de Montevideo; Uruguay
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Dighiero, G.. Instituto Pasteur de Montevideo; Uruguay
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Oppezzo, P.. Universidad de la República; Uruguay. Instituto Pasteur de Montevideo; Uruguay
Materia
LIPOPROTEIN LIPASE
CHRONIC LYMPHOCYTIC LEUKEMIA
DNA METHYLATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/53318
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironmentMoreno, P.Abreu, C.Borge, MercedesPalacios, F.Morande, Pablo ElíasPegazzano, M.Bianchi, S.Landoni, A.I.Agrelo, R.Giordano, Mirta NildaDighiero, G.Gamberale, RominaOppezzo, P.LIPOPROTEIN LIPASECHRONIC LYMPHOCYTIC LEUKEMIADNA METHYLATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have previously demonstrated that lipoprotein lipase (LPL) is associated to an unmutated immunoglobulin profile and clinical poor outcome in Chronic Lymphocytic Leukemia (CLL). Despite the usefulness of LPL for CLL prognosis, its functional role and the molecular mechanism regulating its expression remain elusive. Since interaction of CLL B-cells with tissue microenvironment favors disease progression by promoting malignant B-cell growth and considering that tissue methylation can be altered by environmental factors, we investigated the methylation status of LPL gene and the possibility that its over-expression could be associated to microenvironment signals. By comparing methylation changes in the LPL-CpG island between unmutated and mutated CLL patients, we could demonstrate a clear association between LPL expression and a demethylation process in the CpG island near the promoter region of the LPL gene. This process can be induced by proliferative and specific stimuli,particularly we found that CLL B-cell activation through the CD40 plus IL-4 pathway led to LPL expression and gene demethylation in LPL negative CLL samples. Overall, these results suggest that an epigenetic mechanism, triggered by the microenvironment, regulates LPL expression in CLL cells.Fil: Moreno, P.. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Abreu, C.. Instituto Pasteur de Montevideo; UruguayFil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Palacios, F.. Instituto Pasteur de Montevideo; UruguayFil: Morande, Pablo Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pegazzano, M.. Instituto Pasteur de Montevideo; UruguayFil: Bianchi, S.. Instituto Pasteur de Montevideo; UruguayFil: Landoni, A.I.. Hospital Maciel; UruguayFil: Agrelo, R.. Instituto Pasteur de Montevideo; UruguayFil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Dighiero, G.. Instituto Pasteur de Montevideo; UruguayFil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Oppezzo, P.. Universidad de la República; Uruguay. Instituto Pasteur de Montevideo; UruguayNature Publishing Group2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53318Moreno, P.; Abreu, C.; Borge, Mercedes; Palacios, F.; Morande, Pablo Elías; et al.; Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment; Nature Publishing Group; Leukemia; 27; 3; 3-2013; 721-7250887-6924CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/leu.2012.212info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/leu2012212info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:13:03Zoai:ri.conicet.gov.ar:11336/53318instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:13:04.155CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
title Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
spellingShingle Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
Moreno, P.
LIPOPROTEIN LIPASE
CHRONIC LYMPHOCYTIC LEUKEMIA
DNA METHYLATION
title_short Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
title_full Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
title_fullStr Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
title_full_unstemmed Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
title_sort Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment
dc.creator.none.fl_str_mv Moreno, P.
Abreu, C.
Borge, Mercedes
Palacios, F.
Morande, Pablo Elías
Pegazzano, M.
Bianchi, S.
Landoni, A.I.
Agrelo, R.
Giordano, Mirta Nilda
Dighiero, G.
Gamberale, Romina
Oppezzo, P.
author Moreno, P.
author_facet Moreno, P.
Abreu, C.
Borge, Mercedes
Palacios, F.
Morande, Pablo Elías
Pegazzano, M.
Bianchi, S.
Landoni, A.I.
Agrelo, R.
Giordano, Mirta Nilda
Dighiero, G.
Gamberale, Romina
Oppezzo, P.
author_role author
author2 Abreu, C.
Borge, Mercedes
Palacios, F.
Morande, Pablo Elías
Pegazzano, M.
Bianchi, S.
Landoni, A.I.
Agrelo, R.
Giordano, Mirta Nilda
Dighiero, G.
Gamberale, Romina
Oppezzo, P.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv LIPOPROTEIN LIPASE
CHRONIC LYMPHOCYTIC LEUKEMIA
DNA METHYLATION
topic LIPOPROTEIN LIPASE
CHRONIC LYMPHOCYTIC LEUKEMIA
DNA METHYLATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have previously demonstrated that lipoprotein lipase (LPL) is associated to an unmutated immunoglobulin profile and clinical poor outcome in Chronic Lymphocytic Leukemia (CLL). Despite the usefulness of LPL for CLL prognosis, its functional role and the molecular mechanism regulating its expression remain elusive. Since interaction of CLL B-cells with tissue microenvironment favors disease progression by promoting malignant B-cell growth and considering that tissue methylation can be altered by environmental factors, we investigated the methylation status of LPL gene and the possibility that its over-expression could be associated to microenvironment signals. By comparing methylation changes in the LPL-CpG island between unmutated and mutated CLL patients, we could demonstrate a clear association between LPL expression and a demethylation process in the CpG island near the promoter region of the LPL gene. This process can be induced by proliferative and specific stimuli,particularly we found that CLL B-cell activation through the CD40 plus IL-4 pathway led to LPL expression and gene demethylation in LPL negative CLL samples. Overall, these results suggest that an epigenetic mechanism, triggered by the microenvironment, regulates LPL expression in CLL cells.
Fil: Moreno, P.. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Abreu, C.. Instituto Pasteur de Montevideo; Uruguay
Fil: Borge, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Palacios, F.. Instituto Pasteur de Montevideo; Uruguay
Fil: Morande, Pablo Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Pegazzano, M.. Instituto Pasteur de Montevideo; Uruguay
Fil: Bianchi, S.. Instituto Pasteur de Montevideo; Uruguay
Fil: Landoni, A.I.. Hospital Maciel; Uruguay
Fil: Agrelo, R.. Instituto Pasteur de Montevideo; Uruguay
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Dighiero, G.. Instituto Pasteur de Montevideo; Uruguay
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Oppezzo, P.. Universidad de la República; Uruguay. Instituto Pasteur de Montevideo; Uruguay
description We have previously demonstrated that lipoprotein lipase (LPL) is associated to an unmutated immunoglobulin profile and clinical poor outcome in Chronic Lymphocytic Leukemia (CLL). Despite the usefulness of LPL for CLL prognosis, its functional role and the molecular mechanism regulating its expression remain elusive. Since interaction of CLL B-cells with tissue microenvironment favors disease progression by promoting malignant B-cell growth and considering that tissue methylation can be altered by environmental factors, we investigated the methylation status of LPL gene and the possibility that its over-expression could be associated to microenvironment signals. By comparing methylation changes in the LPL-CpG island between unmutated and mutated CLL patients, we could demonstrate a clear association between LPL expression and a demethylation process in the CpG island near the promoter region of the LPL gene. This process can be induced by proliferative and specific stimuli,particularly we found that CLL B-cell activation through the CD40 plus IL-4 pathway led to LPL expression and gene demethylation in LPL negative CLL samples. Overall, these results suggest that an epigenetic mechanism, triggered by the microenvironment, regulates LPL expression in CLL cells.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/53318
Moreno, P.; Abreu, C.; Borge, Mercedes; Palacios, F.; Morande, Pablo Elías; et al.; Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment; Nature Publishing Group; Leukemia; 27; 3; 3-2013; 721-725
0887-6924
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53318
identifier_str_mv Moreno, P.; Abreu, C.; Borge, Mercedes; Palacios, F.; Morande, Pablo Elías; et al.; Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment; Nature Publishing Group; Leukemia; 27; 3; 3-2013; 721-725
0887-6924
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/leu.2012.212
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/leu2012212
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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