Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00115812" target="_blank" >RIV/00216224:14110/20:00115812 - isvavai.cz</a>
Alternative codes found
RIV/65269705:_____/20:00072707 RIV/00843989:_____/20:E0108384 RIV/61988987:17110/20:A2102601
Result on the web
<a href="https://www.nature.com/articles/s41375-019-0588-4" target="_blank" >https://www.nature.com/articles/s41375-019-0588-4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41375-019-0588-4" target="_blank" >10.1038/s41375-019-0588-4</a>
Alternative languages
Result language
angličtina
Original language name
Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
<a href="/en/project/NV15-29667A" target="_blank" >NV15-29667A: Aberrant plasma cells clonal diversification in immunoglobulin light chain amyloidosis</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia
ISSN
0887-6924
e-ISSN
1476-5551
Volume of the periodical
34
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
15
Pages from-to
589-603
UT code for WoS article
000523481800025
EID of the result in the Scopus database
2-s2.0-85074585646