Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional and circadian distribution profile
A partir d'échantillons sanguins prélevés sur 46 patients atteints d'un myélome multiple, cette étude met en évidence les caractéristiques fonctionnelles, cytogénétiques et phénotypiques des cellules tumorales circulantes ainsi que leur distribution en fonction de l'heure du prélèvement
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 down-regulation (P<.05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). FISH analysis of FACS-sorted CTCs also unraveled different cytogenetic profiles versus paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when co-cultured 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 SDF1 plasma levels and corresponding surface expression of CXCR4 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.
Blood , résumé, 2013