Evidence map›Paper›PMID 41549155›Full record

ArticleAnnals of hematology2026

BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia.

Florian Robert, Cherif Badja, Soraya Boushaki, Andrea Degasperi, Yasin Memari, Sophie Momen, Theodoros I Roumeliotis, Zuza Kozik, Malgorzata Gozdecka, Jyoti Choudhary and 3 more

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Article in Annals of hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

13 authors.

Florian RobertDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK. fr392@cam.ac.uk.
Cherif BadjaDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK.
Soraya BoushakiDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK.
Andrea DegasperiDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK.
Yasin MemariDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK.
Sophie MomenDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK.
Theodoros I RoumeliotisFunctional Proteomics Group, Institute of Cancer Research, Chester Betty Labs, London, SW3 6JB, UK.
Zuza KozikFunctional Proteomics Group, Institute of Cancer Research, Chester Betty Labs, London, SW3 6JB, UK.
Malgorzata GozdeckaCambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.
Jyoti ChoudharyFunctional Proteomics Group, Institute of Cancer Research, Chester Betty Labs, London, SW3 6JB, UK.
George VassiliouCambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge, CB2 0AW, UK.
Gene Cc KohDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK.
Serena Nik-ZainalDepartment of Medical Genetics, Level 6 Addenbrooke's Treatment Centre, Cambridge Biomedical Research Campus, Box 238, Cambridge , CB2 0QQ, UK.

Funding

Cancer Research UK (CRUK) Advanced Clinician Scientist Award C60100/A23916
6 · The paper itself

Abstract

Acute Myeloid Leukemia (AML) remains challenging to treat, especially in cases with mutations in the BCL-6 co-repressor (BCOR), which are associated with poor prognosis and chemo-resistance. In this study, we reveal a synthetic lethal interaction between BCOR and dihydroorotate dehydrogenase (DHODH). We demonstrate that BCOR-deficient cells have a heightened sensitivity to DHODH inhibitors such as brequinar and leflunomide, that are already in clinical use. We confirm that DHODH inhibition selectively induces cell death in BCOR-mutant cells in multiple cellular models, in malignant and non-malignant cells, through chemical and genetic manipulation. Interestingly, we find that the dependency on DHODH does not stem from its role in de novo pyrimidine biosynthesis disruption. Rather, DHODH's role in the electron transport chain, essential for mitigating reactive oxygen species, may be the physiological vulnerability that pushes BCOR-mutant cells toward cell death when DHODH is inhibited. DHODH inhibitors could be repurposed as targeted therapies for BCOR-mutant tumors, offering a promising strategy for precision medicine in AML and other cancers.

Indexed as

Enzyme InhibitorsLeukemia, Myeloid, AcuteMutationOxidoreductases Acting on CH-CH Group DonorsProto-Oncogene ProteinsRepressor ProteinsAntineoplastic AgentsBiphenyl CompoundsCell Line, TumorDihydroorotate DehydrogenaseHumansLeflunomidePyrimidinesQuinaldinesReactive Oxygen SpeciesAntineoplastic AgentsBCOR protein, humanBiphenyl CompoundsbrequinarDihydroorotate DehydrogenaseEnzyme InhibitorsLeflunomideOxidoreductases Acting on CH-CH Group DonorsProto-Oncogene ProteinsPyrimidinesQuinaldinesReactive Oxygen SpeciesRepressor ProteinsAcute myeloid leukemiaBCORDHODHDHODH inhibitionLeukemiaSynthetic lethalityTargeted therapy

Identifiers

PMID41549155
PMCPMC12812770

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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.