ArticleOncogene2018
The PAF complex regulation of Prmt5 facilitates the progression and maintenance of MLL fusion leukemia.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- C6orf223 promotes colorectal cancer growth and metastasis by facilitating PRMT5-MEP50 multiprotein complex assembling.The Journal of clinical investigation · 2025Article
- Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation.PLoS pathogens · 2024Article
- PRMT5 Mediated HIF1α Signaling and Ras-Related Nuclear Protein as Promising Biomarker in Hepatocellular Carcinoma.Biology · 2024Article
- Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms.Therapeutic advances in hematology · 2024Article
- Review
- Targeting MYC in combination with epigenetic regulators induces synergistic anti-leukemic effects in MLLr leukemia and simultaneously improves immunity.Neoplasia (New York, N.Y.) · 2023Article
- Inhibition of histone methyltransferase PRMT5 attenuates cisplatin-induced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway.Journal of pharmaceutical analysis · 2023Article
- Article
- Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies.Cancers · 2022Review
- PRMT5: a putative oncogene and therapeutic target in prostate cancer.Cancer gene therapy · 2022Review
- The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies.Biomolecules · 2021Review
- Protein arginine methylation: from enigmatic functions to therapeutic targeting.Nature reviews. Drug discovery · 2021Review
- A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival.Cell death & disease · 2021Article
- Protein Arginine Methyltransferase 5 Promotes pICln-Dependent Androgen Receptor Transcription in Castration-Resistant Prostate Cancer.Cancer research · 2020Article
- PRMT5 function and targeting in cancer.Cell stress · 2020Review
- MAT2A as Key Regulator and Therapeutic Target inCancers · 2020Article
- Inhibition of DOT1L and PRMT5 promote synergistic anti-tumor activity in a human MLL leukemia model induced by CRISPR/Cas9.Oncogene · 2019Article
- Methionine metabolism in health and cancer: a nexus of diet and precision medicine.Nature reviews. Cancer · 2019Review
- The PAF1c Subunit CDC73 Is Required for Mouse Hematopoietic Stem Cell Maintenance but Displays Leukemia-Specific Gene Regulation.Stem cell reports · 2019Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) is a disease associated with epigenetic dysregulation. 11q23 translocations involving the H3K4 methyltransferase MLL1 (KMT2A) generate oncogenic fusion proteins with deregulated transcriptional potential. The polymerase-associated factor complex (PAFc) is an epigenetic co-activator complex that makes direct contact with MLL fusion proteins and is involved in AML, however, its functions are not well understood. Here, we explored the transcriptional targets regulated by the PAFc that facilitate leukemia by performing RNA-sequencing after conditional loss of the PAFc subunit Cdc73. We found Cdc73 promotes expression of an early hematopoietic progenitor gene program that prevents differentiation. Among the target genes, we confirmed the protein arginine methyltransferase Prmt5 is a direct target that is positively regulated by a transcriptional unit that includes the PAFc, MLL1, HOXA9 and STAT5 in leukemic cells. We observed reduced PRMT5-mediated H4R3me2s following excision of Cdc73 placing this histone modification downstream of the PAFc and revealing a novel mechanism between the PAFc and Prmt5. Knockdown or pharmacologic inhibition of Prmt5 causes a G1 arrest and reduced proliferation resulting in extended leukemic disease latency in vivo. Overall, we demonstrate the PAFc regulates Prmt5 to facilitate leukemic progression and is a potential therapeutic target for AMLs.
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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.