Evidence map›Paper›PMID 35977468›Full record

ArticleCell reports. Medicine2022

hiPSC-derived bone marrow milieu identifies a clinically actionable driver of niche-mediated treatment resistance in leukemia.

Deepali Pal, Helen Blair, Jessica Parker, Sean Hockney, Melanie Beckett, Mankaran Singh, Ricky Tirtakusuma, Ryan Nelson, Hesta McNeill, Sharon H Angel and 14 more

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

Article in Cell reports. Medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

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  5. Epithelial-Mesenchymal Transition in Acute Leukemias.International journal of molecular sciences · 2024
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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

24 authors at 6 institutions in 3 countries.

Deepali PalWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK; Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST UK. Electronic address: deepali.pal@northumbria.ac.uk.
Helen BlairWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Jessica ParkerDepartment of Applied Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST UK.
Sean HockneyDepartment of Applied Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST UK.
Melanie BeckettWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Mankaran SinghWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Ricky TirtakusumaPrincess Maxima Centrum for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.
Ryan NelsonWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Hesta McNeillWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Sharon H AngelWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Aaron WilsonWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Salem NizamiWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Sirintra NakjangBioinformatics Support Unit, William Leech Building, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Peixun ZhouWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Claire SchwabWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Paul SinclairWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Lisa J RussellWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Jonathan CoxheadGenomics Core Facility, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK.
Christina HalseyWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1QH UK.
James M AllanWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Christine J HarrisonWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Anthony V MoormanWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK.
Olaf HeidenreichWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK; Princess Maxima Centrum for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.
Josef VormoorWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Herschel Building Level 6, Brewery Lane, Newcastle upon Tyne, NE1 7RU UK; Princess Maxima Centrum for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands; University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Newcastle University · GBNorthumbria University · GBGenomics (United Kingdom) · GBPrincess Máxima Center · NLUniversity Hospital Heidelberg · DEUniversity of Glasgow · GB

Funding

Cancer Research UK 12788Cancer Research UK 23389Cancer Research UK C27943/A12788Wellcome TrustWellcome Trust 087961Wellcome Trust OSR/0190/DPAL/NUSC
6 · The paper itself

Abstract

Leukemia cells re-program their microenvironment to augment blast proliferation and enhance treatment resistance. Means of clinically targeting such niche-driven treatment resistance remain ambiguous. We develop human induced pluripotent stem cell (hiPSC)-engineered niches to reveal druggable cancer-niche dependencies. We reveal that mesenchymal (iMSC) and vascular niche-like (iANG) hiPSC-derived cells support ex vivo proliferation of patient-derived leukemia cells, affect dormancy, and mediate treatment resistance. iMSCs protect dormant and cycling blasts against dexamethasone, while iANGs protect only dormant blasts. Leukemia proliferation and protection from dexamethasone-induced apoptosis is dependent on cancer-niche interactions mediated by CDH2. Consequently, we test CDH2 antagonist ADH-1 (previously in Phase I/II trials for solid tumors) in a very aggressive patient-derived xenograft leukemia mouse model. ADH-1 shows high in vivo efficacy; ADH-1/dexamethasone combination is superior to dexamethasone alone, with no ADH-1-conferred additional toxicity. These findings provide a proof-of-concept starting point to develop improved, potentially safer therapeutics targeting niche-mediated cancer dependencies in blood cancers.

Indexed as

Induced Pluripotent Stem CellsLeukemiaNeoplasmsAnimalsBone MarrowDexamethasoneDrug Resistance, NeoplasmHumansMiceTumor MicroenvironmentDexamethasonecancer microenvironmentdormancydrugging cancer nicheiPSC-nichetreatment resistance

Identifiers

PMID35977468
PMCPMC9418860
OpenAlexW4291983868

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.