Evidence map›Paper›PMID 38104314›Full record

ArticleCell reports2023

Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth.

Daniel J L Coleman, Peter Keane, Rosario Luque-Martin, Paulynn S Chin, Helen Blair, Luke Ames, Sophie G Kellaway, James Griffin, Elizabeth Holmes, Sandeep Potluri and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

10 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

Daniel J L ColemanInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Peter KeaneInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; School of Biosciences, University of Birmingham, Birmingham B15 2TT, U.K.
Rosario Luque-MartinWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University, Herschel Building, Level 6, Brewery Lane, Newcastle upon Tyne NE1 7RU, UK.
Paulynn S ChinInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Helen BlairWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University, Herschel Building, Level 6, Brewery Lane, Newcastle upon Tyne NE1 7RU, UK.
Luke AmesInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Sophie G KellawayInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
James GriffinInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Elizabeth HolmesInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Sandeep PotluriInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Salam A AssiInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
John BushwellerUniversity of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
Olaf HeidenreichWolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University, Herschel Building, Level 6, Brewery Lane, Newcastle upon Tyne NE1 7RU, UK; Prinses Máxima Centrum for Pediatric Oncology, Postbus 113, 3720 AC Bilthoven, Heidelberglaan 25, 3584CS Utrecht, the Netherlands. Electronic address: o.t.heidenreich@prinsesmaximacentrum.nl.
Peter N CockerillInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: p.n.cockerill@bham.ac.uk.
Constanze BoniferInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: c.bonifer@bham.ac.uk.
University of Birmingham · GBNewcastle University · GBPrincess Máxima Center · NLUniversity of Virginia · US

Funding

Targeted Small Molecule Inhibitors for Inv(16) LeukemiaR01CA234478 · NCI · UNIVERSITY OF VIRGINIA · PI BUSHWELLER, JOHN HACKETT, CASTILLA, LUCIO H. · 2019 to 2023
$3.4M
Medical Research Council MR/P019609/1NCI NIH HHS R01 CA234478
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple gene modules, many of which are transcription factor genes themselves. Here, we hypothesize that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We test this hypothesis using FLT3-ITD-mutated AML as a model and conduct an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict crucial regulatory modules required for AML growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1) module by shRNA and chemical inhibition shows that this transcription factor and its target genes stabilize the GRN of FLT3-ITD+ AML and that its removal leads to GRN collapse and cell death.

Indexed as

Gene Regulatory NetworksLeukemia, Myeloid, Acutefms-Like Tyrosine Kinase 3HumansMutationRegulonRNA, Small InterferingFLT3 protein, humanfms-Like Tyrosine Kinase 3RNA, Small InterferingCP: CancerFLT3-ITD acute myeloid leukemiagene regulatory networksRUNX1 dependencyshRNA drop-out screentranscription factor regulatory modules

Identifiers

PMID38104314
PMCPMC10874628
OpenAlexW4389815011

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.