Expression profile of telomere-associated genes in multiple myeloma

Autores
De la Guardia, Rafael Díaz; Catalina, Purificación; Panero, Julieta; Elosua, Carolina; Pulgarin, Andrés; López, María Belén; Ayllón, Verónica; Ligero, Gertrudis; Slavutsky, Irma Rosa; Leone, Paola E.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To further contribute to the understanding of multiple myeloma, we have focused our research interests on the mechanisms by which tumour plasma cells have a higher survival rate than normal plasma cells. In this article, we study the expression profile of genes involved in the regulation and protection of telomere length, telomerase activity and apoptosis in samples from patients with monoclonal gammopathy of undetermined significance, smouldering multiple myeloma, multiple myeloma (MM) and plasma cell leukaemia (PCL), as well as several human myeloma cell lines (HMCLs). Using conventional cytogenetic and fluorescence in situ hybridization studies, we identified a high number of telomeric associations (TAs). Moreover, telomere length measurements by terminal restriction fragment (TRF) assay showed a shorter mean TRF peak value, with a consistent correlation with the number of TAs. Using gene expression arrays and quantitative PCR we identified the hTERT gene together with 16 other genes directly involved in telomere length maintenance: HSPA9, KRAS, RB1, members of the Small nucleolar ribonucleoproteins family, A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins, and 14-3-3 family. The expression levels of these genes were even higher than those in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), which have unlimited proliferation capacity. In conclusion, the gene signature suggests that MM tumour cells are able to maintain stable short telomere lengths without exceeding the short critical length, allowing cell divisions to continue. We propose that this could be a mechanism contributing to MM tumour cells expansion in the bone marrow (BM). © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Fil: De la Guardia, Rafael Díaz. Universidad de Granada; España
Fil: Catalina, Purificación. Universidad de Granada; España
Fil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Elosua, Carolina. Universidad de Granada; España
Fil: Pulgarin, Andrés. Universidad de Granada; España
Fil: López, María Belén. Universidad de Granada; España
Fil: Ayllón, Verónica. Universidad de Granada; España
Fil: Ligero, Gertrudis. Universidad de Granada; España
Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Leone, Paola E.. Universidad de Granada; España
Materia
Apoptosis
Cell Survival
Chromosomal Instability
Multiple Myeloma
Telomere Length Maintenance
Telomeric Associations
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:11336/52611
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/52611
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Expression profile of telomere-associated genes in multiple myelomaDe la Guardia, Rafael DíazCatalina, PurificaciónPanero, JulietaElosua, CarolinaPulgarin, AndrésLópez, María BelénAyllón, VerónicaLigero, GertrudisSlavutsky, Irma RosaLeone, Paola E.ApoptosisCell SurvivalChromosomal InstabilityMultiple MyelomaTelomere Length MaintenanceTelomeric Associationshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3To further contribute to the understanding of multiple myeloma, we have focused our research interests on the mechanisms by which tumour plasma cells have a higher survival rate than normal plasma cells. In this article, we study the expression profile of genes involved in the regulation and protection of telomere length, telomerase activity and apoptosis in samples from patients with monoclonal gammopathy of undetermined significance, smouldering multiple myeloma, multiple myeloma (MM) and plasma cell leukaemia (PCL), as well as several human myeloma cell lines (HMCLs). Using conventional cytogenetic and fluorescence in situ hybridization studies, we identified a high number of telomeric associations (TAs). Moreover, telomere length measurements by terminal restriction fragment (TRF) assay showed a shorter mean TRF peak value, with a consistent correlation with the number of TAs. Using gene expression arrays and quantitative PCR we identified the hTERT gene together with 16 other genes directly involved in telomere length maintenance: HSPA9, KRAS, RB1, members of the Small nucleolar ribonucleoproteins family, A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins, and 14-3-3 family. The expression levels of these genes were even higher than those in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), which have unlimited proliferation capacity. In conclusion, the gene signature suggests that MM tumour cells are able to maintain stable short telomere lengths without exceeding the short critical length, allowing cell divisions to continue. We propose that this could be a mechanism contributing to MM tumour cells expansion in the bone marrow (BM). © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.Fil: De la Guardia, Rafael Díaz. Universidad de Granada; EspañaFil: Catalina, Purificación. Universidad de Granada; EspañaFil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Elosua, Carolina. Universidad de Granada; EspañaFil: Pulgarin, Andrés. Universidad de Granada; EspañaFil: López, María Belén. Universidad de Granada; EspañaFil: Ayllón, Verónica. Universidad de Granada; EspañaFil: Ligero, Gertrudis. Universidad de Granada; EspañaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Leone, Paola E.. Universidad de Granada; EspañaWiley Blackwell Publishing, Inc2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/52611De la Guardia, Rafael Díaz; Catalina, Purificación; Panero, Julieta; Elosua, Carolina; Pulgarin, Andrés; et al.; Expression profile of telomere-associated genes in multiple myeloma; Wiley Blackwell Publishing, Inc; Journal Of Cellular And Molecular Medicine (print); 16; 12; 12-2012; 3009-30211582-1838CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1582-4934.2012.01628.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1582-4934.2012.01628.xinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393729/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:15:00Zoai:ri.conicet.gov.ar:11336/52611instacron: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:34982025-10-22 11:15:00.766CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Expression profile of telomere-associated genes in multiple myeloma
title Expression profile of telomere-associated genes in multiple myeloma
spellingShingle Expression profile of telomere-associated genes in multiple myeloma
De la Guardia, Rafael Díaz
Apoptosis
Cell Survival
Chromosomal Instability
Multiple Myeloma
Telomere Length Maintenance
Telomeric Associations
title_short Expression profile of telomere-associated genes in multiple myeloma
title_full Expression profile of telomere-associated genes in multiple myeloma
title_fullStr Expression profile of telomere-associated genes in multiple myeloma
title_full_unstemmed Expression profile of telomere-associated genes in multiple myeloma
title_sort Expression profile of telomere-associated genes in multiple myeloma
dc.creator.none.fl_str_mv De la Guardia, Rafael Díaz
Catalina, Purificación
Panero, Julieta
Elosua, Carolina
Pulgarin, Andrés
López, María Belén
Ayllón, Verónica
Ligero, Gertrudis
Slavutsky, Irma Rosa
Leone, Paola E.
author De la Guardia, Rafael Díaz
author_facet De la Guardia, Rafael Díaz
Catalina, Purificación
Panero, Julieta
Elosua, Carolina
Pulgarin, Andrés
López, María Belén
Ayllón, Verónica
Ligero, Gertrudis
Slavutsky, Irma Rosa
Leone, Paola E.
author_role author
author2 Catalina, Purificación
Panero, Julieta
Elosua, Carolina
Pulgarin, Andrés
López, María Belén
Ayllón, Verónica
Ligero, Gertrudis
Slavutsky, Irma Rosa
Leone, Paola E.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Cell Survival
Chromosomal Instability
Multiple Myeloma
Telomere Length Maintenance
Telomeric Associations
topic Apoptosis
Cell Survival
Chromosomal Instability
Multiple Myeloma
Telomere Length Maintenance
Telomeric Associations
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv To further contribute to the understanding of multiple myeloma, we have focused our research interests on the mechanisms by which tumour plasma cells have a higher survival rate than normal plasma cells. In this article, we study the expression profile of genes involved in the regulation and protection of telomere length, telomerase activity and apoptosis in samples from patients with monoclonal gammopathy of undetermined significance, smouldering multiple myeloma, multiple myeloma (MM) and plasma cell leukaemia (PCL), as well as several human myeloma cell lines (HMCLs). Using conventional cytogenetic and fluorescence in situ hybridization studies, we identified a high number of telomeric associations (TAs). Moreover, telomere length measurements by terminal restriction fragment (TRF) assay showed a shorter mean TRF peak value, with a consistent correlation with the number of TAs. Using gene expression arrays and quantitative PCR we identified the hTERT gene together with 16 other genes directly involved in telomere length maintenance: HSPA9, KRAS, RB1, members of the Small nucleolar ribonucleoproteins family, A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins, and 14-3-3 family. The expression levels of these genes were even higher than those in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), which have unlimited proliferation capacity. In conclusion, the gene signature suggests that MM tumour cells are able to maintain stable short telomere lengths without exceeding the short critical length, allowing cell divisions to continue. We propose that this could be a mechanism contributing to MM tumour cells expansion in the bone marrow (BM). © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Fil: De la Guardia, Rafael Díaz. Universidad de Granada; España
Fil: Catalina, Purificación. Universidad de Granada; España
Fil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Elosua, Carolina. Universidad de Granada; España
Fil: Pulgarin, Andrés. Universidad de Granada; España
Fil: López, María Belén. Universidad de Granada; España
Fil: Ayllón, Verónica. Universidad de Granada; España
Fil: Ligero, Gertrudis. Universidad de Granada; España
Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Leone, Paola E.. Universidad de Granada; España
description To further contribute to the understanding of multiple myeloma, we have focused our research interests on the mechanisms by which tumour plasma cells have a higher survival rate than normal plasma cells. In this article, we study the expression profile of genes involved in the regulation and protection of telomere length, telomerase activity and apoptosis in samples from patients with monoclonal gammopathy of undetermined significance, smouldering multiple myeloma, multiple myeloma (MM) and plasma cell leukaemia (PCL), as well as several human myeloma cell lines (HMCLs). Using conventional cytogenetic and fluorescence in situ hybridization studies, we identified a high number of telomeric associations (TAs). Moreover, telomere length measurements by terminal restriction fragment (TRF) assay showed a shorter mean TRF peak value, with a consistent correlation with the number of TAs. Using gene expression arrays and quantitative PCR we identified the hTERT gene together with 16 other genes directly involved in telomere length maintenance: HSPA9, KRAS, RB1, members of the Small nucleolar ribonucleoproteins family, A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins, and 14-3-3 family. The expression levels of these genes were even higher than those in human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), which have unlimited proliferation capacity. In conclusion, the gene signature suggests that MM tumour cells are able to maintain stable short telomere lengths without exceeding the short critical length, allowing cell divisions to continue. We propose that this could be a mechanism contributing to MM tumour cells expansion in the bone marrow (BM). © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
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/11336/52611
De la Guardia, Rafael Díaz; Catalina, Purificación; Panero, Julieta; Elosua, Carolina; Pulgarin, Andrés; et al.; Expression profile of telomere-associated genes in multiple myeloma; Wiley Blackwell Publishing, Inc; Journal Of Cellular And Molecular Medicine (print); 16; 12; 12-2012; 3009-3021
1582-1838
CONICET Digital
CONICET
url http://hdl.handle.net/11336/52611
identifier_str_mv De la Guardia, Rafael Díaz; Catalina, Purificación; Panero, Julieta; Elosua, Carolina; Pulgarin, Andrés; et al.; Expression profile of telomere-associated genes in multiple myeloma; Wiley Blackwell Publishing, Inc; Journal Of Cellular And Molecular Medicine (print); 16; 12; 12-2012; 3009-3021
1582-1838
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1582-4934.2012.01628.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1582-4934.2012.01628.x
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393729/
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
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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