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Abstract: Circulating myeloma tumor cells (CTCs) as defined by the presence of peripheral blood (PB) clonal plasma cells (PCs) are a powerful prognostic marker in multiple myeloma (MM). However, the biological features of CTCs and their pathophysiological role in MM remains unexplored. Here, we investigate the phenotypic, cytogenetic, and functional characteristics as well as the circadian distribution of CTCs vs paired bone marrow (BM) clonal PCs from MM patients. Our results show that CTCs typically represent a unique subpopulation of all BM clonal PCs, characterized by downregulation (P < .05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). Fluorescence in situ hybridization analysis of fluorescence-activated cell sorter?sorted CTCs also unraveled different cytogenetic profiles vs paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when cocultured with BM stromal cells. Most interestingly, CTCs showed a circadian distribution which fluctuates in a similar pattern to that of CD34+ cells, and opposite to stromal cell?derived factor 1 plasma levels and corresponding surface expression of CXC chemokine receptor 4 on clonal PCs, suggesting that in MM, CTCs may egress to PB to colonize/metastasize other sites in the BM during the patients' resting period.
Fuente: Blood, 122(22), 3591-3598
Editorial: American Society of Hematology
Año de publicación: 2013
Nº de páginas: 8
Tipo de publicación: Artículo de Revista
DOI: 10.1182/blood-2013-06-510453
ISSN: 0006-4971,1528-0020
Url de la publicación: https://doi.org/10.1182/blood-2013-06-510453
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PAIVA, BRUNO
PAINO, TERESA
SAYAGUES, JOSE-MARIA
GARAYOA, MERCEDES
SAN-SEGUNDO, LAURA
MARTÍN, MONTSERRAT
MOTA, INES
SANCHEZ, MARÍA-LUZ
BÁRCENA, PALOMA
AIRES-MEJIA, IRENE
CORCHETE, LUIS
JIMENEZ, CRISTINA
GARCIA-SANZ, RAMON
GUTIERREZ, NORMA C.
ENRIQUE MARIA OCIO SAN MIGUEL
MATEOS, MARIA-VICTORIA
VIDRIALES, MARIA-BELEN
ORFAO, ALBERTO
SAN MIGUEL, JESÚS F.
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