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

J 2020

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

GARCES, J. J., M. SIMICEK, M. VICARI, Lucie BROŽOVÁ, L. BURGOS et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{1662865,
   author = {Garces, J. J. and Simicek, M. and Vicari, M. and Brožová, Lucie and Burgos, L. and Bezdekova, R. and Alignani, D. and Calasanz, M. J. and Growkova, K. and Goicoechea, I. and Agirre, X. and Pour, L. and Prosper, F. and Rios, R. and MartinezandLopez, J. and Millacoy, P. and Palomera, L. and Del Orbe, R. and PerezandMontana, A. and Garate, S. and Blanco, L. and Lasa, M. and Maiso, P. and FloresandMontero, J. and SanojaandFlores, L. and Chyra, Zuzana and Vdovin, A. and Sevcikova, T. and Jelinek, T. and Botta, C. and El Omri, H. and Keats, J. and Orfao, A. and Hajek, R. and SanandMiguel, J. F. and Paiva, B.},
   article_location = {London},
   article_number = {2},
   doi = {http://dx.doi.org/10.1038/s41375-019-0588-4},
   keywords = {MINIMAL RESIDUAL DISEASE; CLONAL PLASMA-CELLS; CANCER STEM-CELLS; PROGNOSTIC IMPACT; MONOCLONAL GAMMOPATHY; DRUG-RESISTANCE; FLOW-CYTOMETRY; HIGH-RISK; PROLIFERATION; EXPRESSION},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination},
   url = {https://www.nature.com/articles/s41375-019-0588-4},
   volume = {34},
   year = {2020}
}

TY  - JOUR
ID  - 1662865
AU  - Garces, J. J. - Simicek, M. - Vicari, M. - Brožová, Lucie - Burgos, L. - Bezdekova, R. - Alignani, D. - Calasanz, M. J. - Growkova, K. - Goicoechea, I. - Agirre, X. - Pour, L. - Prosper, F. - Rios, R. - Martinez-Lopez, J. - Millacoy, P. - Palomera, L. - Del Orbe, R. - Perez-Montana, A. - Garate, S. - Blanco, L. - Lasa, M. - Maiso, P. - Flores-Montero, J. - Sanoja-Flores, L. - Chyra, Zuzana - Vdovin, A. - Sevcikova, T. - Jelinek, T. - Botta, C. - El Omri, H. - Keats, J. - Orfao, A. - Hajek, R. - San-Miguel, J. F. - Paiva, B.
PY  - 2020
TI  - Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination
JF  - Leukemia
VL  - 34
IS  - 2
SP  - 589-603
EP  - 589-603
PB  - Nature Publishing Group
SN  - 08876924
KW  - MINIMAL RESIDUAL DISEASE
KW  - CLONAL PLASMA-CELLS
KW  - CANCER STEM-CELLS
KW  - PROGNOSTIC IMPACT
KW  - MONOCLONAL GAMMOPATHY
KW  - DRUG-RESISTANCE
KW  - FLOW-CYTOMETRY
KW  - HIGH-RISK
KW  - PROLIFERATION
KW  - EXPRESSION
UR  - https://www.nature.com/articles/s41375-019-0588-4
L2  - https://www.nature.com/articles/s41375-019-0588-4
N2  - 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.
ER  -

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. \textit{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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