Evidence map›Paper›PMID 36759620›Full record

ArticleNature communications2023

Multi-omics and machine learning reveal context-specific gene regulatory activities of PML::RARA in acute promyelocytic leukemia.

William Villiers, Audrey Kelly, Xiaohan He, James Kaufman-Cook, Abdurrahman Elbasir, Halima Bensmail, Paul Lavender, Richard Dillon, Borbála Mifsud, Cameron S Osborne

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

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

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  14. Function of PML-RARA in Acute Promyelocytic Leukemia.Advances in experimental medicine and biology · 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

10 authors at 3 institutions in 2 countries.

William VilliersDepartment of Medical and Molecular Genetics, King's College London, London, UK.
Audrey KellySchool of Immunology & Microbial Sciences, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
Xiaohan HeDepartment of Medical and Molecular Genetics, King's College London, London, UK.
James Kaufman-CookDepartment of Medical and Molecular Genetics, King's College London, London, UK.
Abdurrahman ElbasirICT Division, College of Science and Engineering, Hamad Bin Khalifa University, Doha, Qatar.
Halima BensmailQatar Computing Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
Paul LavenderSchool of Immunology & Microbial Sciences, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.ORCID 0000-0001-8710-0263
Richard DillonDepartment of Medical and Molecular Genetics, King's College London, London, UK.ORCID 0000-0001-9333-5296
Borbála MifsudCollege of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Doha, Qatar. bmifsud@hbku.edu.qa.ORCID 0000-0003-3429-3094
Cameron S OsborneDepartment of Medical and Molecular Genetics, King's College London, London, UK. cameron.osborne9@gmail.com.ORCID 0000-0003-4126-2499
King's College London · GBHamad bin Khalifa University · QAQueen Mary University of London · GB

Funding

Department of HealthMedical Research Council MR/L016311/1
6 · The paper itself

Abstract

The PML::RARA fusion protein is the hallmark driver of Acute Promyelocytic Leukemia (APL) and disrupts retinoic acid signaling, leading to wide-scale gene expression changes and uncontrolled proliferation of myeloid precursor cells. While known to be recruited to binding sites across the genome, its impact on gene regulation and expression is under-explored. Using integrated multi-omics datasets, we characterize the influence of PML::RARA binding on gene expression and regulation in an inducible PML::RARA cell line model and APL patient ex vivo samples. We find that genes whose regulatory elements recruit PML::RARA are not uniformly transcriptionally repressed, as commonly suggested, but also may be upregulated or remain unchanged. We develop a computational machine learning implementation called Regulatory Element Behavior Extraction Learning to deconvolute the complex, local transcription factor binding site environment at PML::RARA bound positions to reveal distinct signatures that modulate how PML::RARA directs the transcriptional response.

Indexed as

Leukemia, Promyelocytic, AcuteCell LineGene Expression RegulationHumansMultiomicsOncogene Proteins, FusionPromyelocytic Leukemia ProteinRetinoic Acid Receptor alphaTretinoinOncogene Proteins, FusionPML protein, humanPromyelocytic Leukemia ProteinRARA protein, humanRetinoic Acid Receptor alphaTretinoin

Identifiers

PMID36759620
PMCPMC9911410
OpenAlexW4319744415

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.