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Title

Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines

AuthorsPaíno, Teresa ; Sarasquete, María Eugenia; Paiva, Bruno; Krzemiński, Patryk; San-Segundo, Laura; Corchete, Luis A.; Redondo, Alba; Garayoa, Mercedes ; García-Sanz, Ramón; Gutiérrez, Norma Carmen; Ocio, Enrique M. ; San Miguel, Jesús F.
Issue Date2014
PublisherPublic Library of Science
CitationPLoS ONE 9(3): e92378 (2014)
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.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0092378
URIhttp://hdl.handle.net/10261/134660
DOI10.1371/journal.pone.0092378
Identifiersdoi: 10.1371/journal.pone.0092378
issn: 1932-6203
Appears in Collections:(IBMCC) Artículos
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