Krzeminski, P. (Patryk)

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    Phenotypic, genomic and functional characterization reveals no differences between CD138++ and CD138low subpopulations in multiple myeloma cell lines
    (Public Library of Science, 2014) Paino, T. (Teresa); Krzeminski, P. (Patryk); Garayoa, M. (Mercedes); Sarasquete, M.E. (María E.); García-Sanz, R. (Ramón); Ocio, E.M. (Enrique M.); San-Segundo, L. (Laura); Gutierrez, N.C. (Norma C.); Paiva, B. (Bruno); Redondo, A. M. (Alba M.); Corchete, L.A. (Luis A.); San-Miguel, J.F. (Jesús F.)
    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.