Evidence map›Paper›PMID 33806619›Full record

ArticleCells2021

Stroma-Mediated Resistance to S63845 and Venetoclax through MCL-1 and BCL-2 Expression Changes Induced by miR-193b-3p and miR-21-5p Dysregulation in Multiple Myeloma.

Esperanza M Algarín, Dalia Quwaider, Francisco J Campos-Laborie, Andrea Díaz-Tejedor, Pedro Mogollón, Elena Vuelta, Montserrat Martín-Sánchez, Laura San-Segundo, Lorena González-Méndez, Norma C Gutiérrez and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 11 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Esperanza M AlgarínCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.
Dalia QuwaiderCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.
Francisco J Campos-LaborieBioinformatics and Functional Genomics Group, Cancer Research Center (CIC-IBMCC, CSIC/USAL/IBSAL), Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca (USAL) and Institute for Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0002-1213-0457
Andrea Díaz-TejedorCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0003-0802-9767
Pedro MogollónCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0002-6108-0986
Elena VueltaCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.
Montserrat Martín-SánchezCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.
Laura San-SegundoCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0003-2391-5935
Lorena González-MéndezCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.
Norma C GutiérrezCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0001-5834-9510
Ramón García-SanzCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0003-4120-2787
Teresa PaínoCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0002-0201-3572
Javier De Las RivasBioinformatics and Functional Genomics Group, Cancer Research Center (CIC-IBMCC, CSIC/USAL/IBSAL), Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca (USAL) and Institute for Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0002-0984-9946
Enrique M OcioUniversity Hospital Marqués de Valdecilla (IDIVAL), University of Cantabria, 39011 Santander, Spain.ORCID 0000-0002-5765-0085
Mercedes GarayoaCancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.ORCID 0000-0003-2194-2841
Instituto de Investigación Biomédica de Salamanca · ESConsejo Superior de Investigaciones Científicas · ESUniversidad de Cantabria · ES

Funding

Fundación Científica Asociación Española Contra el Cáncer PROYE20047GUTINetwork of Regenerative Medicine and Cellular Therapy of Castilla y LeónRegional Education Council of Junta Castilla y León and European Social FundRegional Health Council of Castilla y León GRS 1604/A/17Spanish ISCIII-FIS and FEDER PI15/02156, PI15/00067, PI18/00591, PI19/01384
6 · The paper itself

Abstract

BH3-mimetics targeting anti-apoptotic proteins such as MCL-1 (S63845) or BCL-2 (venetoclax) are currently being evaluated as effective therapies for the treatment of multiple myeloma (MM). Interleukin 6, produced by mesenchymal stromal cells (MSCs), has been shown to modify the expression of anti-apoptotic proteins and their interaction with the pro-apoptotic BIM protein in MM cells. In this study, we assess the efficacy of S63845 and venetoclax in MM cells in direct co-culture with MSCs derived from MM patients (pMSCs) to identify additional mechanisms involved in the stroma-induced resistance to these agents. MicroRNAs miR-193b-3p and miR-21-5p emerged among the top deregulated miRNAs in myeloma cells when directly co-cultured with pMSCs, and we show their contribution to changes in MCL-1 and BCL-2 protein expression and in the activity of S63845 and venetoclax. Additionally, direct contact with pMSCs under S63845 and/or venetoclax treatment modifies myeloma cell dependence on different BCL-2 family anti-apoptotic proteins in relation to BIM, making myeloma cells more dependent on the non-targeted anti-apoptotic protein or BCL-X

Indexed as

Antineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicDrug Resistance, NeoplasmHumansMultiple MyelomaProto-Oncogene Proteins c-bcl-2PyrimidinesSulfonamidesThiophenesAntineoplastic AgentsBCL2 protein, humanBridged Bicyclo Compounds, HeterocyclicProto-Oncogene Proteins c-bcl-2PyrimidinesS63845SulfonamidesThiophenesvenetoclaxanti-apoptotic proteinsBH3-mimeticsmesenchymal stromal cellsmiR-193miR-21multiple myeloma

Identifiers

PMID33806619
PMCPMC8001939
OpenAlexW3133939589

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.