Evidence map›Paper›PMID 26632274›Full record

ArticleNature communications2015

Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche.

Michelle A Lawson, Michelle M McDonald, Natasa Kovacic, Weng Hua Khoo, Rachael L Terry, Jenny Down, Warren Kaplan, Julia Paton-Hough, Clair Fellows, Jessica A Pettitt and 11 more

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

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
250citing papers in PubMed, 1 pooled it
18.5field-weighted citation impact, top 1% 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

250 citing papers in PubMed, 1 synthesis or guideline pooled it, 382 citations in OpenAlex.

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  16. Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells.Journal of experimental & clinical cancer research : CR · 2026
    Article
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190 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

21 authors at 6 institutions in 3 countries.

Michelle A LawsonDepartment of Oncology, University of Sheffield Medical School, University of Sheffield, Beech Hill Road, Sheffield, South Yorkshire S10 2RX, UK.
Michelle M McDonaldGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Natasa KovacicGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Weng Hua KhooGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Rachael L TerryGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Jenny DownGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Warren KaplanGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Julia Paton-HoughDepartment of Oncology, University of Sheffield Medical School, University of Sheffield, Beech Hill Road, Sheffield, South Yorkshire S10 2RX, UK.
Clair FellowsDepartment of Oncology, University of Sheffield Medical School, University of Sheffield, Beech Hill Road, Sheffield, South Yorkshire S10 2RX, UK.
Jessica A PettittGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
T Neil DearSouth Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia.
Els Van ValckenborghDepartment of Hematology and Immunology, Vrije Universiteit Brussel, Brussels 1090, Belgium.
Paul A BaldockGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Michael J RogersGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Colby L EatonMellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Beech Hill Road, Sheffield, South Yorkshire S10 2RX, UK.
Karin VanderkerkenDepartment of Hematology and Immunology, Vrije Universiteit Brussel, Brussels 1090, Belgium.
Allison R PettitMater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia.
Julian M W QuinnGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Andrew C W ZannettinoSouth Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia.
Tri Giang PhanGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Peter I CroucherGarvan Institute of Medical Research, 384 Victoria Street, Sydney, New South Wales 2010, Australia.
Garvan Institute of Medical Research · AUUniversity of Sheffield · GBSouth Australian Health and Medical Research Institute · AUSt Vincent's Clinic · AUVrije Universiteit Brussel · BETranslational Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and repopulate the tumour. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and reactivation. In this study, we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state that is switched 'on' by engagement with bone-lining cells or osteoblasts, and switched 'off' by osteoclasts remodelling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy that targets dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.

Indexed as

AgedAged, 80 and overAnimalsBone RemodelingCell Line, TumorCoculture TechniquesFemaleHumansMaleMiceMice, Inbred StrainsMiddle AgedMultiple MyelomaOsteoblastsOsteoclasts

Identifiers

PMID26632274
PMCPMC4686867
OpenAlexW2194404144

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.