ArticleEMBO molecular medicine2022
Inhibition of pyrimidine biosynthesis targets protein translation in acute myeloid leukemia.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer.Cancer research · 2026Article
- Targeting nucleotide metabolism and epigenetic regulation to overcome the differentiation blockade in AML.Leukemia research reports · 2026Review
- TP53-dependent antitumor effects of DHODH Inhibition in nasopharyngeal carcinoma.Discover oncology · 2025Article
- Review
- S-adenosylmethionine addiction confers sensitivity to methionine restriction inHaematologica · 2025Article
- Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond.Redox biology · 2025Review
- Guanine nucleotide biosynthesis blockade impairs MLL complex formation and sensitizes leukemias to menin inhibition.Nature communications · 2025Article
- NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation.Leukemia · 2025Article
- Off-Target Inhibition of Human Dihydroorotate Dehydrogenase (ACS pharmacology & translational science · 2024Article
- Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies.International journal of molecular sciences · 2024Review
- FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets.Cancers · 2024Review
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- DHODH: a promising target in the treatment of T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Blockade of de novo pyrimidine biosynthesis triggers autophagic degradation of oncoprotein FLT3-ITD in acute myeloid leukemia.Oncogene · 2023Article
- Leukemic stem cells and therapy resistance in acute myeloid leukemia.Haematologica · 2023Review
- MAC-Seq: Coupling Low-Cost, High-Throughput RNA-Seq with Image-Based Phenotypic Screening in 2D and 3D Cell Models.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Therapeutic targeting of leukemia stem cells in acute myeloid leukemia.Frontiers in oncology · 2023Review
- ENT1 blockade by CNX-774 overcomes resistance to DHODH inhibition in pancreatic cancer.Cancer letters · 2023Article
- Targeting the Leukemic stem cell protein machinery by inhibition of mitochondrial pyrimidine synthesis.EMBO molecular medicine · 2022Article
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17 authors at 5 institutions in 3 countries.
Funding
Abstract
The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) catalyzes one of the rate-limiting steps in de novo pyrimidine biosynthesis, a pathway that provides essential metabolic precursors for nucleic acids, glycoproteins, and phospholipids. DHODH inhibitors (DHODHi) are clinically used for autoimmune diseases and are emerging as a novel class of anticancer agents, especially in acute myeloid leukemia (AML) where pyrimidine starvation was recently shown to reverse the characteristic differentiation block in AML cells. Herein, we show that DHODH blockade rapidly shuts down protein translation in leukemic stem cells (LSCs) and has potent and selective activity against multiple AML subtypes. Moreover, we find that ablation of CDK5, a gene that is recurrently deleted in AML and related disorders, increases the sensitivity of AML cells to DHODHi. Our studies provide important molecular insights and identify a potential biomarker for an emerging strategy to target AML.
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Registered trials
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.