ArticleThe Journal of clinical investigation2016
Targeting methyltransferase PRMT5 eliminates leukemia stem cells in chronic myelogenous leukemia.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 167 citations in OpenAlex.
- Stage-Specific Degradation of Cyclin D3 Orchestrates Myelopoiesis and Restrains Myeloproliferative Neoplasm Development.Cancer research · 2026Article
- Understanding drug resistance in chronic myeloid leukemia through the lens of leukemic stem cell states: insights from single-cell analyses.Haematologica · 2026Review
- Epigenetic plasticity in cancer drug resistance: mechanistic insights and strategies for therapeutic intervention.Acta pharmacologica Sinica · 2026Review
- Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation.Nucleic acids research · 2026Article
- Article
- FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Cell reports. Medicine · 2026Article
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- Review
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- Protein arginine methyltransferase 5 as a novel therapeutic target in solid tumors.Genes & diseases · 2026Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- EZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML.Leukemia · 2025Article
- Review
- PRMT1 Promotes the Self-renewal of Leukemia Stem Cells by Regulating Protein Synthesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting DDX3X eliminates leukemia stem cells in chronic myeloid leukemia by blocking NT5DC2 mRNA translation.Oncogene · 2025Article
- PRMT5-Mediated Arginine Methylation of ACSL4 Attenuates Its Stability and Suppresses Ferroptosis in Renal Cancer.Research (Washington, D.C.) · 2025Article
- Novel targeted therapies in chronic myeloid leukemia.Pharmaceutical science advances · 2024Review
- Interpreting cis-regulatory interactions from large-scale deep neural networks.Nature genetics · 2024Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imatinib-insensitive leukemia stem cells (LSCs) are believed to be responsible for resistance to BCR-ABL tyrosine kinase inhibitors and relapse of chronic myelogenous leukemia (CML). Identifying therapeutic targets to eradicate CML LSCs may be a strategy to cure CML. In the present study, we discovered a positive feedback loop between BCR-ABL and protein arginine methyltransferase 5 (PRMT5) in CML cells. Overexpression of PRMT5 was observed in human CML LSCs. Silencing PRMT5 with shRNA or blocking PRMT5 methyltransferase activity with the small-molecule inhibitor PJ-68 reduced survival, serial replating capacity, and long-term culture-initiating cells (LTC-ICs) in LSCs from CML patients. Further, PRMT5 knockdown or PJ-68 treatment dramatically prolonged survival in a murine model of retroviral BCR-ABL-driven CML and impaired the in vivo self-renewal capacity of transplanted CML LSCs. PJ-68 also inhibited long-term engraftment of human CML CD34+ cells in immunodeficient mice. Moreover, inhibition of PRMT5 abrogated the Wnt/β-catenin pathway in CML CD34+ cells by depleting dishevelled homolog 3 (DVL3). This study suggests that epigenetic methylation modification on histone protein arginine residues is a regulatory mechanism to control self-renewal of LSCs and indicates that PRMT5 may represent a potential therapeutic target against LSCs.
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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.