Evidence map›Paper›PMID 28362441›Full record

ArticleBlood cancer journal2017

Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control.

C Pawlyn, M D Bright, A F Buros, C K Stein, Z Walters, L I Aronson, F Mirabella, J R Jones, M F Kaiser, B A Walker and 7 more

Open access · goldAbstract read
In one paragraph

Article in Blood cancer journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

73 citing papers in PubMed, 104 citations in OpenAlex.

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13 more citing papers are in PubMed but not listed here.

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

17 authors at 5 institutions in 2 countries.

C PawlynThe Institute of Cancer Research, London, UK.ORCID 0000-0002-7190-0028
M D BrightThe Institute of Cancer Research, London, UK.
A F BurosMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
C K SteinMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Z WaltersThe Institute of Cancer Research, London, UK.
L I AronsonThe Institute of Cancer Research, London, UK.
F MirabellaThe Institute of Cancer Research, London, UK.ORCID 0000-0003-3785-6868
J R JonesThe Institute of Cancer Research, London, UK.
M F KaiserThe Institute of Cancer Research, London, UK.
B A WalkerMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
G H JacksonDepartment of Haematology, Newcastle University, Newcastle, UK.
P A ClarkeThe Institute of Cancer Research, London, UK.
P L BergsagelMayo Clinic Arizona, Scottsdale, AZ, USA.ORCID 0000-0003-1523-7388
P WorkmanThe Institute of Cancer Research, London, UK.
M ChesiMayo Clinic Arizona, Scottsdale, AZ, USA.
G J MorganThe Institute of Cancer Research, London, UK.
F E DaviesThe Institute of Cancer Research, London, UK.
Institute of Cancer Research · GBRoyal Marsden NHS Foundation Trust · GBUniversity of Arkansas for Medical Sciences · USMayo Clinic in Arizona · USNewcastle University · GB

Funding

Project 4: Targeting Resistance to T-Cell Directed Therapy in Multiple MyelomaP50CA186781 · NCI · MAYO CLINIC ARIZONA · PI Rafael Fonseca · 2015 to 2026
$25.5M
Project 3 - Modeling Proteasome Inhibitor Response and Resistance in Cell Lines and Patient Samples with Single Cell Analysis of SubpopulationsU54CA224018 · NCI · MAYO CLINIC ARIZONA · PI BERGSAGEL, PETER LEIF · 2017 to 2021
$6.0M
PQD2 Rational Combination of Standard Agents and Immunotherapy to Treat MyelomaR01CA190045 · NCI · MAYO CLINIC ARIZONA · PI CHESI, MARTA · 2014 to 2017
$1.4M
Cancer Research UK C20826/A1210Medical Research Council G0100132NCI NIH HHS P50 CA186781NCI NIH HHS R01 CA190045Wellcome Trust 102363/Z/13/Z
6 · The paper itself

Abstract

Myeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly defined high-risk patients who continue to do badly. Novel therapeutic approaches are, therefore, required. A growing number of epigenetic inhibitors are now available including EZH2 inhibitors that are in early-stage clinical trials for treatment of haematological and other cancers with EZH2 mutations or in which overexpression has been correlated with poor outcomes. For the first time, we have identified and validated a robust and independent deleterious effect of high EZH2 expression on outcomes in myeloma patients. Using two chemically distinct small-molecule inhibitors, we demonstrate a reduction in myeloma cell proliferation with EZH2 inhibition, which leads to cell cycle arrest followed by apoptosis. This is mediated via upregulation of cyclin-dependent kinase inhibitors associated with removal of the inhibitory H3K27me3 mark at their gene loci. Our results suggest that EZH2 inhibition may be a potential therapeutic strategy for the treatment of myeloma and should be investigated in clinical studies.

Indexed as

Gene ExpressionApoptosisBiomarkersCell Cycle CheckpointsCell Line, TumorCell ProliferationCell SurvivalEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticGene Expression ProfilingHistonesHumansKaplan-Meier EstimateMesenchymal Stem CellsMultiple MyelomaPhenotypeBiomarkersEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesRNA, Messenger

Identifiers

PMID28362441
PMCPMC5380911
OpenAlexW2603203825

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.