Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination

Cirino Botta, Diego Alignani, Patricia Maiso, Ludek Pour, Sonia Garate, Bruno Paiva, Juan Flores-Montero, Albert Perez-Montaña, Michal Simicek, Cirino Botta, Ibai Goicoechea, Tereza Sevcikova, Lucie Brozova, Zuzana Chyra, Tomas Jelinek, Katerina Growkova, Renata Bezdekova, Leire Burgos, Luzalba Sanoja-Flores, Rafael Del OrbeXabier Agirre, Jesus F. San-Miguel, Pamela Millacoy, Roman Hajek, Laura Blanco, Alexander Vdovin, Marco Vicari, Zuzana Chyra, Juan-Jose Garcés, Roman Hajek, Halima El Omri, Felipe Prosper, Luis Palomera, Maria-Jose Calasanz, Rafael Rios, Jonathan Keats, Joaquin Martinez-Lopez, Alberto Orfao, Marta Lasa

Risultato della ricerca: Articlepeer review

11 Citazioni (Scopus)

Abstract

The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 patients, we found high correlation in gene expression at single-cell and bulk levels (r ≥ 0.94, P = 10−16), with only 55 genes differentially expressed between CTCs and BM tumor cells. CTCs overexpressed genes involved in inflammation, hypoxia, or epithelial–mesenchymal transition, whereas genes related with proliferation were downregulated in CTCs. The cancer stem cell marker CD44 was overexpressed in CTCs, and its knockdown significantly reduced migration of MM cells towards SDF1-α and their adhesion to fibronectin. Approximately half (29/55) of genes differentially expressed in CTCs were prognostic in patients with newly-diagnosed myeloma (n = 553; CoMMpass). In a multivariate analysis including the R-ISS, overexpression of CENPF and LGALS1 was significantly associated with inferior survival. Altogether, these results help understanding the presence of CTCs in PB and suggest that hypoxic BM niches together with a pro-inflammatory microenvironment induce an arrest in proliferation, forcing tumor cells to circulate in PB and seek other BM niches to continue growing.
Lingua originaleEnglish
pagine (da-a)589-603
Numero di pagine15
RivistaLeukemia
Volume34
Stato di pubblicazionePublished - 2020

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2700.2730???
  • ???subjectarea.asjc.1300.1306???

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