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

Jens G. Lohr*, Sora Kim, Joshua Gould, Birgit Knoechel, Yotam Drier, Matthew J. Cotton, Daniel Gray, Nicole Birrer, Bang Wong, Gavin Ha, Cheng Zhong Zhang, Guangwu Guo, Matthew Meyerson, Andrew J. Yee, Jesse S. Boehm, Noopur Raje, Todd R. Golub

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


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 ofMMgenomic evolution on therapy by serial bone marrowbiopsy 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 recapitulateMMin the bone marrow. We demonstrate that CTCs provide the same genetic information as bonemarrowMM 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.2016

Original languageAmerican English
Article number363ra147
JournalScience Translational Medicine
Issue number363
StatePublished - 2 Nov 2016
Externally publishedYes

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