Research ArticleCancer

Genetic interrogation of circulating multiple myeloma cells at single-cell resolution

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Science Translational Medicine  02 Nov 2016:
Vol. 8, Issue 363, pp. 363ra147
DOI: 10.1126/scitranslmed.aac7037

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Single-cell approach to multiple myeloma

Multiple myeloma is a cancer of plasma cells in the bone marrow, and it remains very difficult to treat. Unfortunately, it is hard to tell when a patient is developing chemotherapy resistance because monitoring response to treatment in this cancer normally requires a bone marrow biopsy, an invasive and painful procedure that cannot be repeated frequently. Lohr et al. now demonstrate that circulating tumor cells in peripheral blood of multiple myeloma patients can provide the same genetic information as bone marrow samples, and sometimes more. This finding suggests that noninvasive monitoring of peripheral blood samples in multiple myeloma should be useful for tracking patients’ response to therapy and optimizing the treatment approach for each patient.


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.

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