title: Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
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.
authors.affiliation: Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Paíno
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: María E
authors.initials: ME
authors.lastname: Sarasquete
authors.affiliation: Clínica Universidad de Navarra; Centro de Investigaciones Médicas Aplicadas (CIMA), Pamplona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Patryk
authors.initials: P
authors.lastname: Krzeminski
authors.affiliation: Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: San-Segundo
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Corchete
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Redondo
authors.affiliation: Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Garayoa
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.affiliation: Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain; Hospital Universitario de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
authors.forename: Enrique M
authors.initials: EM
authors.lastname: Ocio
authors.affiliation: Clínica Universidad de Navarra; Centro de Investigaciones Médicas Aplicadas (CIMA), Pamplona, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San-Miguel
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D045744:Cell Line, Tumor; D056915:DNA Copy Number Variations; D004317:Doxorubicin / Q000494:pharmacology; D064593:Heterografts; D006801:Humans; D016130:Immunophenotyping; D008558:Melphalan / Q000494:pharmacology; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology / Q000503:physiopathology*; D014411:Neoplastic Stem Cells; D010641:Phenotype; D010950:Plasma Cells / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid; D011719:Pyrazines / Q000494:pharmacology; D053668:Syndecan-1 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D053668:Syndecan-1; D000069286:Bortezomib; D004317:Doxorubicin; D008558:Melphalan