Evidence map›Paper›PMID 42585304›Full record

ArticleScience advances2026

RNA terminal uridylyl transferases are druggable vulnerabilities in AML but are dispensable for normal hematopoiesis.

Christopher Mapperley, Elise Georges, Ali A Azar, Yuka Kabayama, Hannah Lawson, Iwo Kucinski, Derek George, Joana Campos, Corey Fyfe, Jozef Durko and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. 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.

No citing paper in PubMed yet.

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

30 authors.

Christopher MapperleyDivision of Cancer Biology, The Institute of Cancer Research, London, UK.ORCID 0000-0002-2059-7006
Elise GeorgesBarts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0009-0000-9255-4999
Ali A AzarBarts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0009-0008-8294-1811
Yuka KabayamaCentre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.ORCID 0000-0001-8340-7196
Hannah LawsonDivision of Cancer Biology, The Institute of Cancer Research, London, UK.ORCID 0009-0000-4129-0014
Iwo KucinskiDepartment of Haematology, Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.ORCID 0000-0002-9385-0359
Derek GeorgeDivision of Cancer Biology, The Institute of Cancer Research, London, UK.
Joana CamposDivision of Cancer Biology, The Institute of Cancer Research, London, UK.
Corey FyfeRedona Therapeutics, Watertown, MA. USA.ORCID 0009-0005-6315-1425
Jozef DurkoBarts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-2395-8946
Wei Y ChanThe Francis Crick Institute, London, UK.ORCID 0000-0003-0471-2059
Lewis AllenDivision of Cancer Biology, The Institute of Cancer Research, London, UK.
Babak JazayeriCentre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.ORCID 0009-0004-6686-5434
Edward BlackerBarts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0009-0008-1601-8260
Louie N van de LagemaatBarts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-2947-1557
Aurelien TrippDivision of Cell and Molecular Biology, The Institute of Cancer Research, London, UK.ORCID 0000-0002-7547-4441
Theodoros I RoumeliotisDivision of Cell and Molecular Biology, The Institute of Cancer Research, London, UK.ORCID 0000-0002-3354-5643
Giulia GuiducciBarts Cancer Institute, Queen Mary University of London, London, UK.
Eleanor HerbertDepartment of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, UK.ORCID 0000-0002-2216-7771
Jasmin ParisThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
Jyoti ChoudharyDivision of Cell and Molecular Biology, The Institute of Cancer Research, London, UK.ORCID 0000-0003-0881-5477
George PoulogiannisDivision of Cell and Molecular Biology, The Institute of Cancer Research, London, UK.
Robert M CampbellRedona Therapeutics, Watertown, MA. USA.
Marcos MorganCentre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-3549-0375
Lovorka StojicBarts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0001-6691-3396
Folkert J Van WervenThe Francis Crick Institute, London, UK.ORCID 0000-0002-6685-2084
Douglas VernimmenDivision of Genome Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-1308-9919
Berthold GöttgensDepartment of Haematology, Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.ORCID 0000-0001-6302-5705
Dónal O'CarrollCentre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-8626-2217
Kamil R KrancDivision of Cancer Biology, The Institute of Cancer Research, London, UK.ORCID 0000-0001-7547-4989

Funding

Wellcome Trust
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is an aggressive hematological malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Current treatments often fail to eradicate AML; therefore, new therapeutic strategies are essential. Here, we reveal that RNA terminal uridylyl transferase enzymes 4 and 7 (TUT4/7) are druggable therapeutic targets, whose genetic deletion suppresses AML growth, induces apoptosis, and improves the survival in leukemic mouse models. Notably, a preclinical TUT4/7 inhibitor promotes cell death in samples from patients with AML and synergizes with venetoclax. Mechanistically, TUT4/7 inactivation suppresses mevalonate pathway gene expression, compromising the cholesterol synthesis pathway. Current AML therapies often cause severe hematopoietic toxicity. Although

Indexed as

HematopoiesisLeukemia, Myeloid, AcuteRNA NucleotidyltransferasesAnimalsApoptosisBridged Bicyclo Compounds, HeterocyclicDisease Models, AnimalEnzyme InhibitorsHematopoietic Stem CellsHumansMiceSulfonamidesBridged Bicyclo Compounds, HeterocyclicEnzyme InhibitorsRNA NucleotidyltransferasesSulfonamidesvenetoclax

Identifiers

PMID42585304
PMCPMC13464643

What Socratic holds

Textmetadata
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 Socratic graph.