Evidence map›Paper›PMID 37503022›Full record

ArticlebioRxiv : the preprint server for biology2023

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 · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

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 B152TT, UK.
Peter KeaneInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK.
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 B152TT, 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 B152TT, UK.
Sophie G KellawayInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK.
James GriffinInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK.
Elizabeth HolmesInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK.
Sandeep PotluriInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK.
Salam A AssiInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK.
John BushwellerUniversity of Virginia, 1340 Jefferson Park Ave, 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.
Peter N CockerillInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK.
Constanze BoniferInstitute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, 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/S021469/1NCI NIH HHS R01 CA234478
6 · The paper itself

Abstract

AML is a heterogenous disease caused by different mutations. We have previously shown that each mutational sub-type develops its specific gene regulatory network (GRN) with transcription factors interacting with multiple gene modules, many of which are transcription factor genes themselves. Here we hypothesized that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We tested this hypothesis using FLT3-ITD mutated AML as a model and conducted an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict identifying crucial regulatory modules required for AML but not normal cellular 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.

Identifiers

PMID37503022
PMCPMC10370108
OpenAlexW4384829242

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.