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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.
Fuente: PLoS One, 2014, 9(3), e92378
Año de publicación: 2014
Nº de páginas: 12
Tipo de publicación: Artículo de Revista
DOI: 10.1371/journal.pone.0092378
ISSN: 1932-6203
Url de la publicación: https://doi.org/10.1371/journal.pone.0092378
Consultar en UCrea Leer publicación
PAÍNO, TERESA
SARASQUETE, MARÍA E.
PAIVA, BRUNO
KRZEMINSKI, PATRYK
SAN-SEGUNDO, LAURA
CORCHETE, LUIS A.
REDONDO, ALBA
GARAYOA, MERCEDES
GARCÍA-SANZ, RAMÓN
GUTIÉRREZ, NORMA C.
ENRIQUE MARIA OCIO SAN MIGUEL
SAN-MIGUEL, JESÚS F.
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