Evidence map›Paper›PMID 29276143›Full record

ArticleCell stem cell2018

Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML.

Delfim Duarte, Edwin D Hawkins, Olufolake Akinduro, Heather Ang, Katia De Filippo, Isabella Y Kong, Myriam Haltalli, Nicola Ruivo, Lenny Straszkowski, Stephin J Vervoort and 12 more

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

Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers.

0numbers the graph read from it
0cells of the map it votes in
196citing papers in PubMed
20.3field-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

196 citing papers in PubMed, 316 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 8 institutions in 4 countries.

Delfim DuarteDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK; The Francis Crick Institute, WC2A 3LY London, UK. Electronic address: delfimd@med.up.pt.
Edwin D HawkinsDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK; The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
Olufolake AkinduroDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK.
Heather AngDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK.
Katia De FilippoInflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, SW7 2AZ London, UK.
Isabella Y KongThe Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
Myriam HaltalliDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK.
Nicola RuivoDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK.
Lenny StraszkowskiStem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia.
Stephin J VervoortSir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
Catriona McLeanDepartment of Haematology, Alfred Hospital, Melbourne, VIC 3004, Australia.
Tom S WeberHamilton Institute, Maynooth University, Maynooth, Ireland.
Reema KhorshedDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK.
Chiara PirilloDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK.
Andrew WeiDepartment of Haematology, Alfred Hospital, Melbourne, VIC 3004, Australia.
Saravana K RamasamyInstitute of Clinical Sciences, Imperial College London, W12 0NN London, UK.
Anjali P KusumbeKennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford OX3 7FY, UK.
Ken DuffyHamilton Institute, Maynooth University, Maynooth, Ireland.
Ralf H AdamsMax Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, 48149 Munster, Germany; University of Münster, Faculty of Medicine, 48149 Munster, Germany.
Louise E PurtonStem Cell Regulation Unit, St. Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Department of Medicine, The University of Melbourne, Fitzroy, VIC 3065, Australia.
Leo M CarlinInflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, SW7 2AZ London, UK; Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
Cristina Lo CelsoDepartment of Life Sciences, Sir Alexander Fleming Building, Imperial College London, SW7 2AZ London, UK; The Francis Crick Institute, WC2A 3LY London, UK. Electronic address: c.lo-celso@imperial.ac.uk.
Imperial College London · GBNational University of Ireland, Maynooth · IEThe Alfred Hospital · AUUniversity of Melbourne · AUPeter MacCallum Cancer Centre · AUSt Vincents Institute of Medical Research · AUUniversity of Münster · DEUniversity of Oxford · GB

Funding

Biotechnology and Biological Sciences Research Council BB/I004033/1Cancer Research UK 11831Cancer Research UK 23983Cancer Research UK A23983Cancer Research UK C36195/A1183Medical Research Council MC_UP_1605/1Medical Research Council MR/M01245X/1Medical Research Council MR/P02209X/1Medical Research Council MR/PO2209X/1Wellcome Trust 201356/Z/16/ZWellcome Trust 202300/Z/16/Z
6 · The paper itself

Abstract

Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression leads to differential remodeling of vasculature in central and endosteal bone marrow regions. Endosteal AML cells produce pro-inflammatory and anti-angiogenic cytokines and gradually degrade endosteal endothelium, stromal cells, and osteoblastic cells, whereas central marrow remains vascularized and splenic vascular niches expand. Remodeled endosteal regions have reduced capacity to support non-leukemic HSCs, correlating with loss of normal hematopoiesis. Preserving endosteal endothelium with the small molecule deferoxamine or a genetic approach rescues HSCs loss, promotes chemotherapeutic efficacy, and enhances survival. These findings suggest that preventing degradation of the endosteal vasculature may improve current paradigms for treating AML.

Indexed as

Stem Cell NicheAnimalsBone MarrowCell CountHematopoiesisHematopoietic Stem CellsHumansIntravital MicroscopyLeukemia, Myeloid, AcuteMice, Inbred C57BLSpleenStromal CellsTime FactorsTumor Microenvironmentacute myeloid leukemiablood vesselsbone marrowendosteumhematopoietic stem cellsintravital microscopymicroenvironmentosteoblaststransendothelial migration

Identifiers

PMID29276143
PMCPMC5766835
OpenAlexW2775836849

What OpenQuestion holds

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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.