Genetic Interrogation of Circulating Multiple Myeloma Cells at Single-cell Resolution

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2016 Nov 4

PMID 27807282

Citations 85

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Advancements in Multiple Myeloma Research: High-Throughput Sequencing Technologies, Omics, and the Role of Artificial Intelligence.

Gutierrez-Gonzalez A, Del Hierro I, Cariaga-Martinez A Biology (Basel). 2024; 13(11).

PMID: 39596878 PMC: 11592186. DOI: 10.3390/biology13110923.

In vitro models of the crosstalk between multiple myeloma and stromal cells recapitulate the mild NF-κB activation observed in vivo.

Colombo F, Guzzeloni V, Kizilirmak C, Brambilla F, Garcia-Manteiga J, Tascini A Cell Death Dis. 2024; 15(10):731.

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Navigating the clinical landscape: Update on the diagnostic and prognostic biomarkers in multiple myeloma.

Raghunathachar S, Krishnamurthy K, Gopalaiah L, Abhijith D, Prashant A, Parichay S Mol Biol Rep. 2024; 51(1):972.

PMID: 39249557 DOI: 10.1007/s11033-024-09892-w.

Single-cell genomics-based immune and disease monitoring in blood malignancies.

Rathgeber A, Ludwig L, Penter L Clin Hematol Int. 2024; 6(2):62-84.

PMID: 38884110 PMC: 11180218. DOI: 10.46989/001c.117961.

Liquid Biopsies as Non-Invasive Tools for Mutation Profiling in Multiple Myeloma: Application Potential, Challenges, and Opportunities.

Heestermans R, Schots R, De Becker A, Van Riet I Int J Mol Sci. 2024; 25(10).

PMID: 38791247 PMC: 11121516. DOI: 10.3390/ijms25105208.

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