Genetic interrogation of circulating multiple myeloma cells at single-cell resolution
Menée à partir notamment de 24 échantillons sanguins prélevés sur des patients atteints d'un myélome multiple, cette étude met en évidence la faisabilité d'une méthode permettant d'isoler des cellules circulantes tumorales et d'effectuer une analyse génomique ou transcriptomique à l'échelle d'une seule cellule, puis démontre l'intérêt de cette méthode pour surveiller, sans avoir recours à une biopsie de la moelle osseuse, l'émergence de cellules tumorales résistantes aux traitements
Multiple myeloma (MM) remains an incurable disease, with a treatment-refractory state eventually developing in all patients. Constant clonal evolution and genetic heterogeneity of MM are a likely explanation for the emergence of drug-resistant disease. Monitoring of MM genomic evolution on therapy by serial bone marrow biopsy is unfortunately impractical because it involves an invasive and painful procedure. We describe how noninvasive and highly sensitive isolation and characterization of circulating tumor cells (CTCs) from peripheral blood at single-cell resolution recapitulate MM in the bone marrow. We demonstrate that CTCs provide the same genetic information as bone marrow MM cells and even reveal mutations with greater sensitivity than bone marrow biopsies in some cases. Single CTC RNA sequencing enables classification of MM and quantitative assessment of genes that are relevant for prognosis. We propose that the genomic characterization of CTCs should be included in clinical trials to follow the emergence of resistant subclones after MM therapy.
Science Translational Medicine , résumé, 2015