Scientific publications

Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma

Jun 1, 2020 | Magazine: Leukemia

Juan-José Garcés, Gabriel Bretones, Leire Burgos, Rafael Valdes-Mas, Noemi Puig, Maria-Teresa Cedena, Diego Alignani, Idoia Rodriguez, Diana Álvarez Puente, Miguel-García Álvarez, Ibai Goicoechea, Sara Rodriguez, Maria-Jose Calasanz, Xabier Agirre, Juan Flores-Montero, Luzalba Sanoja-Flores, Paula Rodriguez-Otero, Rafael Rios, Joaquin Martinez-Lopez, Pamela Millacoy, Luis Palomera, Rafael Del Orbe, Albert Pérez-Montaña, Halima El Omri, Felipe Prosper, Maria-Victoria Mateos, Laura Rosiñol, Joan Blade, Juan-Jose Lahuerta, Alberto Orfao, Carlos Lopez-Otin, Jesus F San Miguel, Bruno Paiva, GEM/PETHEMA (Grupo Español de Mieloma/Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group


Multiple myeloma (MM) patients undergo repetitive bone marrow (BM) aspirates for genetic characterization. Circulating tumor cells (CTCs) are detectable in peripheral blood (PB) of virtually all MM cases and are prognostic, but their applicability for noninvasive screening has been poorly investigated. Here, we used next-generation flow (NGF) cytometry to isolate matched CTCs and BM tumor cells from 53 patients and compared their genetic profile.

In eight cases, tumor cells from extramedullary (EM) plasmacytomas were also sorted and whole-exome sequencing was performed in the three spatially distributed tumor samples. CTCs were detectable by NGF in the PB of all patients with MM. Based on the cancer cell fraction of clonal and subclonal mutations, we found that ~22% of CTCs egressed from a BM (or EM) site distant from the matched BM aspirate.

Concordance between BM tumor cells and CTCs was high for chromosome arm-level copy number alterations (≥95%) though not for translocations (39%). All high-risk genetic abnormalities except one t(4;14) were detected in CTCs whenever present in BM tumor cells. Noteworthy, ≥82% mutations present in BM and EM clones were detectable in CTCs. Altogether, these results support CTCs for noninvasive risk-stratification of MM patients based on their numbers and genetic profile.

CITATION  Leukemia. 2020 Nov;34(11):3007-3018. doi: 10.1038/s41375-020-0883-0. Epub 2020 Jun 1.