BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia.
1/5 보강
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.
APA
Robert F, Badja C, et al. (2026). BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia.. Annals of hematology, 105(1), 32. https://doi.org/10.1007/s00277-026-06773-z
MLA
Robert F, et al.. "BCOR mutations define a therapeutic vulnerability to DHODH Inhibition in acute myeloid leukemia.." Annals of hematology, vol. 105, no. 1, 2026, pp. 32.
PMID
41549155 ↗
Abstract 한글 요약
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.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- Leukemia
- Myeloid
- Acute
- Dihydroorotate Dehydrogenase
- Proto-Oncogene Proteins
- Oxidoreductases Acting on CH-CH Group Donors
- Mutation
- Reactive Oxygen Species
- Cell Line
- Tumor
- Leflunomide
- Enzyme Inhibitors
- Biphenyl Compounds
- Quinaldines
- Repressor Proteins
- Acute myeloid leukemia
- BCOR
- DHODH
- DHODH inhibition
- Synthetic lethality
- Targeted therapy
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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