ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Integration Analysis of Bayesian and Machine Learning for Heterogeneity, Biomarkers, and Optimal Combination Regimens of Pucotenlimab in Solid Tumors.Cancer medicine · 2026Article
- Review
- PCsRNAdb: a comprehensive resource of small noncoding RNAs across cancers.Nucleic acids research · 2026Article
- Butyrate modifies epigenetic and immune pathways in peripheral mononuclear cells from children with neurodevelopmental disorders associated with chromatin dysregulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Unveiling Interleukin-40: A Novel Regulator of Macrophage and B Cell Function in Allergic Asthma.International journal of biological sciences · 2026Article
- Epstein-Barr virus infection shapes the genetic, transcriptomic, and immune microenvironment landscape of Burkitt lymphoma.Infectious agents and cancer · 2025Article
- Similar Normalizing Effect of HSP70 and YB-1 Stress Proteins on the Brain Transcription of a Mouse Model of Alzheimer's Disease.Molecular neurobiology · 2025Article
- Chidamide and cytarabine synergistically treat acute myeloid leukemia: inhibiting ribosome biogenesis via the MYC-RRP9 pathway.Cell death & disease · 2025Article
- Prognostic Risk Model of Megakaryocyte-Erythroid Progenitor (MEP) Signature Based on AHSP and MYB in Acute Myeloid Leukemia.Biomedicines · 2025Article
- Whole genome sequencing and single-cell transcriptomics identify KMT2D inactivation as a potential new driver for pituitary tumors: a case report.BJC reports · 2025Article
- Identification of novel genetic mutations for the treatment prognostication of canine lymphoma.NPJ precision oncology · 2025Article
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening.Nature communications · 2025Article
- Elucidating AML ribosome biogenesis reshaping prognostic assessment and immune microenvironment integrated single-cell and bulk RNA analysis.Frontiers in immunology · 2025Article
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.Genome research · 2024Article
- Article
- Genomic hallmarks and therapeutic targets of ribosome biogenesis in cancer.Briefings in bioinformatics · 2024Article
- The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice.bioRxiv : the preprint server for biology · 2023Article
- KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
23 authors at 2 institutions in 2 countries.
Funding
Abstract
KMT2C and KMT2D are the most frequently mutated epigenetic genes in human cancers. While KMT2C is identified as a tumor suppressor in acute myeloid leukemia (AML), the role of KMT2D remains unclear in this disease, though its loss promotes B cell lymphoma and various solid cancers. Here, it is reported that KMT2D is downregulated or mutated in AML and its deficiency, through shRNA knockdown or CRISPR/Cas9 editing, accelerates leukemogenesis in mice. Hematopoietic stem and progenitor cells and AML cells with Kmt2d loss have significantly enhanced ribosome biogenesis and consistently, enlarged nucleolus, increased rRNA and protein synthesis rates. Mechanistically, it is found that KMT2D deficiency leads to the activation of the mTOR pathway in both mouse and human AML cells. Kmt2d directly regulates the expression of Ddit4, a negative regulator of the mTOR pathway. Consistent with the abnormal ribosome biogenesis, it is shown that CX-5461, an inhibitor of RNA polymerase I, significantly restrains the growth of AML with Kmt2d loss in vivo and extends the survival of leukemic mice. These studies validate KMT2D as a de facto tumor suppressor in AML and reveal an unprecedented vulnerability to ribosome biogenesis inhibition.
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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.