@article{10902/32320,
year = {2014},
url = {https://hdl.handle.net/10902/32320},
abstract = {Despite 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.},
organization = {This 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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.},
publisher = {PLoS One, 2014, 9(3), e92378},
title = {Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines},
author = {Paíno, Teresa and Sarasquete, María E. and Paiva, Bruno and Krzeminski, Patryk and San-Segundo, Laura and Corchete, Luis A. and Redondo, Alba and Garayoa, Mercedes and García-Sanz, Ramón and Gutiérrez, Norma C. and Ocio San Miguel, Enrique María and San-Miguel, Jesús F.},
}