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dc.contributor.authorPaíno, Teresa-
dc.contributor.authorSarasquete, María Eugenia-
dc.contributor.authorPaiva, Bruno-
dc.contributor.authorKrzemiński, Patryk-
dc.contributor.authorSan-Segundo, Laura-
dc.contributor.authorCorchete, Luis A.-
dc.contributor.authorRedondo, Alba-
dc.contributor.authorGarayoa, Mercedes-
dc.contributor.authorGarcía-Sanz, Ramón-
dc.contributor.authorGutiérrez, Norma Carmen-
dc.contributor.authorOcio, Enrique M.-
dc.contributor.authorSan Miguel, Jesús F.-
dc.identifierdoi: 10.1371/journal.pone.0092378-
dc.identifierissn: 1932-6203-
dc.identifier.citationPLoS ONE 9(3): e92378 (2014)-
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-
dc.description.abstractDespite recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease potentially due to the presence of resistant myeloma cancer stem cells (MM-CSC). Although the presence of clonogenic cells in MM was described three decades ago, the phenotype of MM-CSC is still controversial, especially with respect to the expression of syndecan-1 (CD138). Here, we demonstrate the presence of two subpopulations - CD138++ (95-99%) and CD138low (1-5%) - in eight MM cell lines. To find out possible stem-cell-like features, we have phenotypically, genomic and functionally characterized the two subpopulations. Our results show that the minor CD138low subpopulation is morphologically identical to the CD138++ fraction and does not represent a more immature B-cell compartment (with lack of CD19, CD20 and CD27 expression). Moreover, both subpopulations have similar gene expression and genomic profiles. Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID mice shows that CD138++ as well as CD138low cells have self-renewal potential and they are phenotypically interconvertible. Overall, our results differ from previously published data in MM cell lines which attribute a B-cell phenotype to MM-CSC. Future characterization of clonal plasma cell subpopulations in MM patients' samples will guarantee the discovery of more reliable markers able to discriminate true clonogenic myeloma cells.-
dc.description.sponsorshipThis work was supported by the Cooperative Research Thematic Network (RTICs; RD06/0020/0006), the “Junta de Castilla y León. Consejería de Sanidad” (GRS 391/B/09), the “Ministerio de Ciencia e Innovación” (PS09/01897), the “Fundación Memoria D. Samuel Solórzano Barruso” (FS/2-2010) and Asociación Española Contra el Cáncer (AECC)(GCB120981SAN).-
dc.publisherPublic Library of Science-
dc.relation.isversionofPublisher's version-
dc.titlePhenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines-
dc.description.versionPeer Reviewed-
dc.contributor.funderAsociación Española Contra el Cáncer-
dc.contributor.funderFundación Memoria de D. Samuel Solorzano Barruso-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderRed Temática de Investigación Cooperativa en Cáncer (España)-
dc.contributor.funderJunta de Castilla y León-
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