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dc.contributor.author Panero, Julieta
dc.contributor.author Stella, Flavia
dc.contributor.author Schutz, Natalia
dc.contributor.author Fantl, Dorotea Beatriz
dc.contributor.author Slavutsky, Irma Rosa
dc.date.available 2018-04-19T20:03:31Z
dc.date.issued 2015-09-14
dc.identifier.citation Panero, Julieta; Stella, Flavia; Schutz, Natalia; Fantl, Dorotea Beatriz; Slavutsky, Irma Rosa; Differential expression of non-shelterin genes associated with high telomerase levels and telomere shortening in plasma cell disorders; Public Library of Science; Plos One; 10; 9; 14-9-2015; e0137972- e0137972
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/11336/42744
dc.description.abstract Telomerase, shelterin proteins and various interacting factors, named non-shelterin proteins, are involved in the regulation of telomere length (TL). Altered expression of any of these telomere-associated genes can lead to telomere dysfunction, causing genomic instability and disease development. In this study, we investigated the expression profile of a set of non-shelterin genes involved in essential processes such as replication (RPA1), DNA damage repair pathways (MRE11-RAD50-NBS1) and stabilization of telomerase complex (DKC1), in 35 patients with monoclonal gammopathy of undetermined significance (MGUS) and 40 cases with multiple myeloma (MM). Results were correlated with hTERT expression, TL and clinical parameters. Overall, a significant increase in DKC1, RAD50, MRE11, NBS1 and RPA1 expression along with an upregulation of hTERT in MM compared with MGUS was observed (p≤0.032). Interestingly, in both entities higher mRNA levels of non-shelterin genes was found to be associated with short TLs and increased hTERT expression. Significant differences were observed for DKC1 in MM (p≤0.03), suggesting an important role for this gene in the maintenance of short telomeres by telomerase in myeloma plasma cells. With regard to clinical associations, we observed a significant increase in DKC1, RAD50, MRE11 and RPA1 expression in MM cases with high bone marrow infiltration (p≤0.03) and a tendency towards cases with advanced ISS stage, providing the first evidence of non-shelterin genes associated to risk factors in MM. Taken together, our findings provide new insights into the intricate mechanisms by which telomere-associated proteins collaborate in the maintenance of plasma cells immortalization and suggest a role for the upregulation of these genes in the progression of the disease.
dc.format application/pdf
dc.language.iso eng
dc.publisher Public Library of Science
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject MULTIPLE MYELOMA
dc.subject TELOMERES
dc.subject NON-SHELTERIN COMPLEX
dc.subject GENE EXPRESSION
dc.subject.classification Inmunología
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Differential expression of non-shelterin genes associated with high telomerase levels and telomere shortening in plasma cell disorders
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2018-04-09T19:05:22Z
dc.journal.volume 10
dc.journal.number 9
dc.journal.pagination e0137972- e0137972
dc.journal.pais Estados Unidos
dc.journal.ciudad San Francisco
dc.description.fil Fil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil Fil: Stella, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil Fil: Schutz, Natalia. Hospital Italiano; Argentina
dc.description.fil Fil: Fantl, Dorotea Beatriz. Hospital Italiano; Argentina
dc.description.fil Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.journal.title Plos One
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137972
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0137972
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/pmid/26366868
dc.conicet.fuente individual


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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)