Evidence map›Paper›PMID 23847194›Full record

ArticleBlood2013

RARα2 expression confers myeloma stem cell features.

Ye Yang, Jumei Shi, Giulia Tolomelli, Hongwei Xu, Jiliang Xia, He Wang, Wen Zhou, Yi Zhou, Satyabrata Das, Zhimin Gu and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 73 citations in OpenAlex.

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  16. Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020
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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

13 authors at 3 institutions in 3 countries.

Ye YangDepartment of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Jumei Shi
Giulia Tolomelli
Hongwei Xu
Jiliang Xia
He Wang
Wen Zhou
Yi Zhou
Satyabrata Das
Zhimin Gu
Dana Levasseur
Fenghuang Zhan
Guido Tricot
University of Iowa · USPoliclinico S.Orsola-Malpighi · ITShanghai Tenth People's Hospital · CN

Funding

NEK2 Over-expression Causes Drug Resistance in MyelomaR01CA152105 · NCI · UNIVERSITY OF UTAH · PI ZHAN, FENGHUANG · 2010 to 2014
$1.5M
Gene expression profiling vs MRD assessment in MyelomaR01CA115399 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI TRICOT, GUIDO J. · 2006 to 2011
$1.3M
Retinoid Based Treatment Approaches to Target the Myeloma Stem CellR21CA143887 · NCI · UNIVERSITY OF UTAH · PI ZHAN, FENGHUANG · 2010 to 2011
$354k
NCI NIH HHS R01 CA115399NCI NIH HHS R01CA115399NCI NIH HHS R01 CA152105NCI NIH HHS R01CA152105NCI NIH HHS R21 CA143887NCI NIH HHS R21CA143887
6 · The paper itself

Abstract

We previously demonstrated that RARα2 expression is increased in CD138 selected plasma cells of relapsed multiple myelomas (MMs), and increased expression was linked to poor prognosis in newly diagnosed MM patients. In the present study, we demonstrate that increased RARα2 confers myeloma stem cell features. Higher expression of RARα2 was identified in the multiple myeloma stem cell (MMSC) fraction. Overexpression of RARα2 in bulk MM cell lines resulted in: 1) increased drug resistance; 2) increased clonogenic potential; 3) activation of both Wnt and Hedgehog (Hh) pathways; 4) increased side population and aldehyde dehydrogenase levels; and 5) increased expression of embryonic stem cell genes. The opposite effects were seen with RARα2 knockdown. We demonstrate that RARα2 induces drug resistance by activating the drug efflux pump gene ABCC3 and anti-apoptotic Bcl-2 family members. Inhibition of Wnt signaling or ABCC3 function could overcome drug resistance in RARα2 overexpressing MM cells. We also showed that in the 5TGM1 mouse model, targeting of the Wnt and Hh pathways using CAY10404, cyclopamine, or itraconazole significantly reduced the myeloma tumor burden and increased survival. Targeting RARα2 or its downstream signaling pathways provides a potential strategy to eliminate MMSC.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsATP-Binding Cassette, Sub-Family C ProteinsCell Line, TumorCell SurvivalGene Expression ProfilingHedgehog ProteinsHumansIsoxazolesItraconazoleMiceMultiple MyelomaNeoplastic Stem CellsPlasma CellsPrognosisProto-Oncogene Proteins c-bcl-23-(4-methylsulfonylphenyl)-4-phenyl-5-trifluoromethylisoxazoleATP-Binding Cassette, Sub-Family C ProteinscyclopamineHedgehog ProteinsIsoxazolesItraconazolemultidrug resistance-associated protein 3Proto-Oncogene Proteins c-bcl-2RARA protein, humanRara protein, mouseReceptors, Retinoic AcidRetinoic Acid Receptor alphaSulfonesSyndecan-1Veratrum AlkaloidsWnt Proteins

Identifiers

PMID23847194
PMCPMC3750340
OpenAlexW2062719570

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.