GARCES, J. J., M. SIMICEK, M. VICARI, Lucie BROŽOVÁ, L. BURGOS, R. BEZDEKOVA, D. ALIGNANI, M. J. CALASANZ, K. GROWKOVA, I. GOICOECHEA, X. AGIRRE, L. POUR, F. PROSPER, R. RIOS, J. MARTINEZ-LOPEZ, P. MILLACOY, L. PALOMERA, R. DEL ORBE, A. PEREZ-MONTANA, S. GARATE, L. BLANCO, M. LASA, P. MAISO, J. FLORES-MONTERO, L. SANOJA-FLORES, Zuzana CHYRA, A. VDOVIN, T. SEVCIKOVA, T. JELINEK, C. BOTTA, H. EL OMRI, J. KEATS, A. ORFAO, R. HAJEK, J. F. SAN-MIGUEL and B. PAIVA. Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination. Leukemia. London: Nature Publishing Group, 2020, vol. 34, No 2, p. 589-603. ISSN 0887-6924. Available from: https://dx.doi.org/10.1038/s41375-019-0588-4.
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Basic information
Original name Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination
Authors GARCES, J. J. (724 Spain), M. SIMICEK (203 Czech Republic), M. VICARI (380 Italy), Lucie BROŽOVÁ (203 Czech Republic, belonging to the institution), L. BURGOS (724 Spain), R. BEZDEKOVA (203 Czech Republic), D. ALIGNANI (724 Spain), M. J. CALASANZ (724 Spain), K. GROWKOVA (203 Czech Republic), I. GOICOECHEA (724 Spain), X. AGIRRE (724 Spain), L. POUR (203 Czech Republic), F. PROSPER (724 Spain), R. RIOS (724 Spain), J. MARTINEZ-LOPEZ (724 Spain), P. MILLACOY (724 Spain), L. PALOMERA, R. DEL ORBE (724 Spain), A. PEREZ-MONTANA (724 Spain), S. GARATE (724 Spain), L. BLANCO (724 Spain), M. LASA (724 Spain), P. MAISO (840 United States of America), J. FLORES-MONTERO (724 Spain), L. SANOJA-FLORES (724 Spain), Zuzana CHYRA (203 Czech Republic, belonging to the institution), A. VDOVIN (203 Czech Republic), T. SEVCIKOVA (203 Czech Republic), T. JELINEK (203 Czech Republic), C. BOTTA (724 Spain), H. EL OMRI (724 Spain), J. KEATS (724 Spain), A. ORFAO (724 Spain), R. HAJEK (203 Czech Republic), J. F. SAN-MIGUEL (724 Spain) and B. PAIVA (724 Spain, guarantor).
Edition Leukemia, London, Nature Publishing Group, 2020, 0887-6924.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30204 Oncology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 11.528
RIV identification code RIV/00216224:14110/20:00115812
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1038/s41375-019-0588-4
UT WoS 000523481800025
Keywords in English MINIMAL RESIDUAL DISEASE; CLONAL PLASMA-CELLS; CANCER STEM-CELLS; PROGNOSTIC IMPACT; MONOCLONAL GAMMOPATHY; DRUG-RESISTANCE; FLOW-CYTOMETRY; HIGH-RISK; PROLIFERATION; EXPRESSION
Tags 14119612, podil, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 31/8/2020 12:06.
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-a 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.
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