ArticleEMBO molecular medicine2023
IMPDH inhibition activates TLR-VCAM1 pathway and suppresses the development of MLL-fusion leukemia.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting IMPDH to inhibit SAMHD1 inCell cycle (Georgetown, Tex.) · 2026Article
- Mycophenolate mofetil induces angiogenesis disorders in zebrafish embryos by inhibiting the mitogen-activated protein kinase signaling pathway.Biological research · 2026Article
- IMP metabolic mechanisms and IMPDH targeting strategies in tumor metabolic reprogramming and therapy (Review).International journal of molecular medicine · 2026Review
- Expanding the targeted protein degradation approach with small molecule chimeras directed to the 26S proteasome.Nature communications · 2026Article
- IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Molecular oncology · 2026Article
- IMPDH and GTP Metabolism in Cancer: Mechanisms, Regulation, and Translational Scope.Cancer science · 2025Review
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Machine Learning-Based Predictive Modeling Maximizes the Efficacy of mTOR/p53 Co-Targeting Therapy Against AML.Cancer science · 2025Article
- A stem cell differentiation model reveals two alternative fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation.Communications biology · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- USP5 deubiquitinates and stabilizes IMPDH2, to promote hepatocellular carcinoma progression.Oncogene · 2025Article
- IMPDH2's Central Role in Cellular Growth and Diseases: A Potential Therapeutic Target.Cell proliferation · 2025Review
- Acute Myeloid Leukemia Genome Characterization Study and Subtype Classification Employing Feature Selection and Bayesian Networks.Biomedicines · 2025Article
- Article
- Guanine nucleotide biosynthesis blockade impairs MLL complex formation and sensitizes leukemias to menin inhibition.Nature communications · 2025Article
- Lessons from the physiological role of guanosine in neurodegeneration and cancer: Toward a multimodal mechanism of action?Purinergic signalling · 2025Review
- Inosine monophosphate dehydrogenase 2 (IMPDH2) modulates response to therapy and chemo-resistance in triple negative breast cancer.Scientific reports · 2025Article
- Endovascular management of primary long-segment inferior vena cava occlusion: treatment strategies and clinical outcomes.Frontiers in pharmacology · 2025Article
- Targeting protein tyrosine phosphatase non-receptor type 6 (PTPN6) as a therapeutic strategy in acute myeloid leukemia.Cell biology and toxicology · 2024Article
- De novo GTP synthesis is a metabolic vulnerability for the interception of brain metastases.Cell reports. Medicine · 2024Article
Corrections and comments
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Authors and funding
31 authors at 8 institutions in 2 countries.
Funding
Abstract
Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in de novo guanine nucleotide synthesis pathway. Although IMPDH inhibitors are widely used as effective immunosuppressants, their antitumor effects have not been proven in the clinical setting. Here, we found that acute myeloid leukemias (AMLs) with MLL-fusions are susceptible to IMPDH inhibitors in vitro. We also showed that alternate-day administration of IMPDH inhibitors suppressed the development of MLL-AF9-driven AML in vivo without having a devastating effect on immune function. Mechanistically, IMPDH inhibition induced overactivation of Toll-like receptor (TLR)-TRAF6-NF-κB signaling and upregulation of an adhesion molecule VCAM1, which contribute to the antileukemia effect of IMPDH inhibitors. Consequently, combined treatment with IMPDH inhibitors and the TLR1/2 agonist effectively inhibited the development of MLL-fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL-fusion AMLs and potentially other aggressive tumors with active TLR signaling.
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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 OpenQuestion graph.