{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T19:10:02Z","timestamp":1767985802698,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Adult T-cell leukemia\/lymphoma (ATLL) is an aggressive T-cell malignancy caused by persistent infection with human T-cell leukemia virus type 1 (HTLV-1). ATLL remains difficult to treat despite intensive chemotherapy, antiviral therapy, and hematopoietic stem cell transplantation. The limited durability of current treatment strategies highlights the need for mechanism-based therapeutic approaches. Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that regulates transcription, RNA splicing, DNA damage responses, and immune signaling through symmetric dimethylation of histone and non-histone substrates. PRMT5 is frequently overexpressed across hematologic and solid tumors. Preclinical studies indicate that PRMT5 expression is elevated during HTLV-1-mediated T-cell transformation and that pharmacologic inhibition of PRMT5 selectively impairs the survival and transformation of infected T cells in vitro and in vivo. In this review, we highlight the current understanding of PRMT5 biology in cancer, summarize preclinical studies supporting PRMT5 as a therapeutic target in ATLL, and discuss key challenges to future clinical translation. We also discuss emerging approaches such as rational combination therapies and tumor-selective PRMT5 inhibitors as potential paths toward treatment for ATLL.<\/jats:p>","DOI":"10.3390\/v18010094","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:15:50Z","timestamp":1767968150000},"page":"94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting PRMT5 in Adult T-Cell Leukemia\/Lymphoma: Opportunities and Challenges"],"prefix":"10.3390","volume":"18","author":[{"given":"Kyle","family":"Ernzen","sequence":"first","affiliation":[{"name":"Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-3705","authenticated-orcid":false,"given":"Amanda R.","family":"Panfil","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1073\/pnas.79.6.2031","article-title":"Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease","volume":"79","author":"Yoshida","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-cell leukemia: Clinical and hematologic features of 16 cases","volume":"50","author":"Uchiyama","year":"1977","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gessain, A., and Cassar, O. (2012). Epidemiological Aspects and World Distribution of HTLV-1 Infection. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00388"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nrc2111","article-title":"Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation","volume":"7","author":"Matsuoka","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1111\/bjh.15234","article-title":"Can we reduce the incidence of adult T-cell leukaemia\/lymphoma? Cost-effectiveness of human T-lymphotropic virus type 1 (HTLV-1) antenatal screening in the United Kingdom","volume":"184","author":"Malik","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.coviro.2016.08.009","article-title":"Human T-cell leukemia virus-associated malignancy","volume":"20","author":"Panfil","year":"2016","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0145-2126(93)90061-O","article-title":"Characteristics of chemotherapy-induced clinical remission in long survivors with aggressive adult T-cell leukemia\/lymphoma","volume":"17","author":"Tsukasaki","year":"1993","journal-title":"Leuk. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/978-1-4615-1601-9_3","article-title":"HTLV-I associated leukemia\/lymphoma: Epidemiology, biology, and treatment","volume":"104","author":"Siegel","year":"2001","journal-title":"Cancer Treat. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1200\/JOP.2017.021907","article-title":"Adult T-Cell Leukemia\/Lymphoma","volume":"13","author":"Ratner","year":"2017","journal-title":"J. Oncol. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1179\/102453312X13336169155330","article-title":"Adult T-cell leukemia-lymphoma","volume":"17","author":"Tsukasaki","year":"2012","journal-title":"Hematology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1182\/blood-2009-09-242347","article-title":"Long-term study of indolent adult T-cell leukemia-lymphoma","volume":"115","author":"Takasaki","year":"2010","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1200\/JCO.18.00501","article-title":"Revised Adult T-Cell Leukemia-Lymphoma International Consensus Meeting Report","volume":"37","author":"Cook","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.tibs.2011.09.001","article-title":"Versatility of PRMT5-induced methylation in growth control and development","volume":"36","author":"Karkhanis","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17960","DOI":"10.1073\/pnas.1209814109","article-title":"Crystal structure of the human PRMT5:MEP50 complex","volume":"109","author":"Antonysamy","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molcel.2016.11.003","article-title":"Arginine Methylation: The Coming of Age","volume":"65","author":"Blanc","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1007\/s00018-015-1847-9","article-title":"The PRMT5 arginine methyltransferase: Many roles in development, cancer and beyond","volume":"72","author":"Stopa","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.gendis.2019.06.002","article-title":"PRMT5 in gene regulation and hematologic malignancies","volume":"6","author":"Zhu","year":"2019","journal-title":"Genes. Dis."},{"key":"ref_19","first-page":"536","article-title":"Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells","volume":"40","author":"Jeon","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/1746-1596-8-201","article-title":"Cellular localization of protein arginine methyltransferase-5 correlates with grade of lung tumors","volume":"8","author":"Shilo","year":"2013","journal-title":"Diagn. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1010428317695917","DOI":"10.1177\/1010428317695917","article-title":"Elevated expression of protein arginine methyltransferase 5 predicts the poor prognosis of breast cancer","volume":"39","author":"Wu","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.canlet.2018.04.019","article-title":"Protein arginine methyltransferase 5 promotes lung cancer metastasis via the epigenetic regulation of miR-99 family\/FGFR3 signaling","volume":"427","author":"Jing","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1016\/j.bbadis.2018.05.015","article-title":"Protein arginine methyltransferase 5-mediated epigenetic silencing of IRX1 contributes to tumorigenicity and metastasis of gastric cancer","volume":"1864","author":"Liu","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/pin.12338","article-title":"High nuclear expression of protein arginine methyltransferase-5 is a potentially useful marker to estimate submucosal invasion in endoscopically resected early colorectal carcinoma","volume":"65","author":"Pak","year":"2015","journal-title":"Pathol. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6319","DOI":"10.1158\/1078-0432.CCR-18-1270","article-title":"PRMT5 Circular RNA Promotes Metastasis of Urothelial Carcinoma of the Bladder through Sponging miR-30c to Induce Epithelial-Mesenchymal Transition","volume":"24","author":"Chen","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s10549-017-4597-6","article-title":"PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in breast cancer","volume":"168","author":"Wang","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115484","DOI":"10.1016\/j.celrep.2025.115484","article-title":"PRMT5-mediated methylation of METTL3 promotes cisplatin resistance in ovarian cancer by facilitating DNA repair mechanisms","volume":"44","author":"Xia","year":"2025","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/jcb.22432","article-title":"Methylation of histone H3 and H4 by PRMT5 regulates ribosomal RNA gene transcription","volume":"109","author":"Majumder","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1038\/sj.emboj.7601794","article-title":"Low levels of miR-92b\/96 induce PRMT5 translation and H3R8\/H4R3 methylation in mantle cell lymphoma","volume":"26","author":"Pal","year":"2007","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9630","DOI":"10.1128\/MCB.24.21.9630-9645.2004","article-title":"Human SWI\/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes","volume":"24","author":"Pal","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6262","DOI":"10.1128\/MCB.00923-08","article-title":"Protein arginine methyltransferase 5 suppresses the transcription of the RB family of tumor suppressors in leukemia and lymphoma cells","volume":"28","author":"Wang","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Yan, F., Alinari, L., Lustberg, M., Martin, L.K., Nowicki, O., Wu, X., Yu, B., Gordon, K., Wolfson, A., and Ryu, J. (2010, January 17\u201321). Targeting protein arginine methyltransferase 5 (PRMT5) enzyme over expression in high grade astrocytomas. Proceedings of the 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, USA.","DOI":"10.1158\/1538-7445.AM10-1584"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nchembio.422","article-title":"Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding","volume":"6","author":"Guo","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.1093\/nar\/gkq1264","article-title":"A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage","volume":"39","author":"He","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5601","DOI":"10.1093\/nar\/gky291","article-title":"PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes","volume":"46","author":"Rehman","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1016\/j.celrep.2018.08.002","article-title":"PRMT5 Regulates DNA Repair by Controlling the Alternative Splicing of Histone-Modifying Enzymes","volume":"24","author":"Hamard","year":"2018","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7181","DOI":"10.1038\/s41388-019-0937-9","article-title":"Inhibition of DOT1L and PRMT5 promote synergistic anti-tumor activity in a human MLL leukemia model induced by CRISPR\/Cas9","volume":"38","author":"Secker","year":"2019","journal-title":"Oncogene"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1016\/j.celrep.2017.11.096","article-title":"PRMT5 Is a Critical Regulator of Breast Cancer Stem Cell Function via Histone Methylation and FOXP1 Expression","volume":"21","author":"Chiang","year":"2017","journal-title":"Cell Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.1172\/JCI85239","article-title":"Targeting methyltransferase PRMT5 eliminates leukemia stem cells in chronic myelogenous leukemia","volume":"126","author":"Jin","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eaaz5683","DOI":"10.1126\/scitranslmed.aaz5683","article-title":"PRMT5 control of cGAS\/STING and NLRC5 pathways defines melanoma response to antitumor immunity","volume":"12","author":"Kim","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"199","DOI":"10.15698\/cst2020.08.228","article-title":"PRMT5 function and targeting in cancer","volume":"4","author":"Kim","year":"2020","journal-title":"Cell Stress."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6211","DOI":"10.1182\/bloodadvances.2023009906","article-title":"PRMT5 inhibition drives therapeutic vulnerability to combination treatment with BCL-2 inhibition in mantle cell lymphoma","volume":"7","author":"Hwang","year":"2023","journal-title":"Blood Adv."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41408-023-00799-6","article-title":"Exploiting PRMT5 as a target for combination therapy in mantle cell lymphoma characterized by frequent ATM and TP53 mutations","volume":"13","author":"Che","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/leu.2017.206","article-title":"Genetic deletion or small-molecule inhibition of the arginine methyltransferase PRMT5 exhibit anti-tumoral activity in mouse models of MLL-rearranged AML","volume":"32","author":"Kaushik","year":"2018","journal-title":"Leukemia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8407","DOI":"10.1021\/acs.jmedchem.3c00250","article-title":"Targeting Arginine Methyltransferase PRMT5 for Cancer Therapy: Updated Progress and Novel Strategies","volume":"66","author":"Zheng","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Panfil, A.R., Al-Saleem, J., Howard, C.M., Mates, J.M., Kwiek, J.J., Baiocchi, R.A., and Green, P.L. (2015). PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival. Viruses, 8.","DOI":"10.3390\/v8010007"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nchembio.1810","article-title":"A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models","volume":"11","author":"Kuplast","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"v159","DOI":"10.1093\/annonc\/mdz244","article-title":"METEOR-1: A phase I study of GSK3326595, a first-in-class protein arginine methyltransferase 5 (PRMT5) inhibitor, in advanced solid tumours","volume":"30","author":"Siu","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1182\/blood-2019-130337","article-title":"A phase I\/II study to investigate the safety and clinical activity of the protein arginine methyltransferase 5 inhibitor GSK3326595 in subjects with myelodysplastic syndrome and acute myeloid leukemia","volume":"134","author":"Watts","year":"2019","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ernzen, K., Melvin, C., Yu, L., Phelps, C., Niewiesk, S., Green, P.L., and Panfil, A.R. (2023). The PRMT5 inhibitor EPZ015666 is effective against HTLV-1-transformed T-cell lines in vitro and in vivo. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1101544"},{"key":"ref_51","first-page":"49","article-title":"Animal Models Utilized in HTLV-1 Research","volume":"4","author":"Panfil","year":"2013","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ichikawa, T., Suekane, A., Nakahata, S., Iha, H., Shimoda, K., Murakami, T., and Morishita, K. (2024). Inhibition of PRMT5\/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2(low) Adult T-Cell Leukemia\/Lymphoma. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052842"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1016\/j.bbadis.2019.07.001","article-title":"The regulation of NDRG2 expression during ATLL development after HTLV-1 infection","volume":"1865","author":"Ichikawa","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lee, K.W., Lim, S., and Kim, K.D. (2022). The Function of N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Negative Regulator in Tumor Cell Metastasis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169365"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12841","DOI":"10.1038\/srep12841","article-title":"Loss of NDRG2 enhanced activation of the NF-\u03baB pathway by PTEN and NIK phosphorylation for ATL and other cancer development","volume":"5","author":"Ichikawa","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1038\/ncomms4393","article-title":"Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers","volume":"5","author":"Nakahata","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"118615","DOI":"10.1016\/j.bbamcr.2019.118615","article-title":"Novel PRMT5-mediated arginine methylations of HSP90A are essential for maintenance of HSP90A function in NDRG2(low) ATL and various cancer cells","volume":"1867","author":"Ichikawa","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1742-4690-9-64","article-title":"Comparative host protein interactions with HTLV-1 p30 and HTLV-2 p28: Insights into difference in pathobiology of human retroviruses","volume":"9","author":"Doueiri","year":"2012","journal-title":"Retrovirology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nm984","article-title":"HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication","volume":"10","author":"Nicot","year":"2004","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9885","DOI":"10.1128\/JVI.75.20.9885-9895.2001","article-title":"Human T-lymphotropic virus type 1 p30(II) regulates gene transcription by binding CREB binding protein\/p300","volume":"75","author":"Zhang","year":"2001","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/1742-4690-4-49","article-title":"Human T-lymphotropic virus type-1 p30 alters cell cycle G2 regulation of T lymphocytes to enhance cell survival","volume":"4","author":"Datta","year":"2007","journal-title":"Retrovirology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/1476-4598-9-302","article-title":"HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression","volume":"9","author":"Baydoun","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5897","DOI":"10.1182\/blood-2010-08-304600","article-title":"Human T-lymphotropic type 1 virus p30 inhibits homologous recombination and favors unfaithful DNA repair","volume":"117","author":"Baydoun","year":"2011","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.4049\/jimmunol.1601702","article-title":"PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis","volume":"198","author":"Webb","year":"2017","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e57306","DOI":"10.15252\/embr.202357306","article-title":"PRMT5 links lipid metabolism to contractile function of skeletal muscles","volume":"24","author":"Kim","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1172\/JCI81749","article-title":"Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis","volume":"125","author":"Liu","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00018-024-05154-x","article-title":"PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells","volume":"81","author":"Wang","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1101\/gad.606110","article-title":"Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency","volume":"24","author":"Tee","year":"2010","journal-title":"Genes. Dev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"102961","DOI":"10.1016\/j.esmoop.2024.102961","article-title":"A phase I study to evaluate the safety, pharmacokinetics, and pharmacodynamics of PF-06939999 (PRMT5 inhibitor) in patients with selected advanced or metastatic tumors with high incidence of splicing factor gene mutations","volume":"9","author":"Rodon","year":"2024","journal-title":"ESMO Open"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.annonc.2025.08.3757","article-title":"Phase Ib and dose-expansion study of GSK3326595, a PRMT5 inhibitor as monotherapy and in combination with pembrolizumab in patients with advanced cancers","volume":"36","author":"Gounder","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3592","DOI":"10.1158\/1078-0432.CCR-23-0092","article-title":"Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors","volume":"29","author":"Vieito","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1182\/bloodadvances.2023010554","article-title":"Resistance to PRMT5-targeted therapy in mantle cell lymphoma","volume":"8","author":"Long","year":"2024","journal-title":"Blood Adv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1200\/JCO.2008.18.2428","article-title":"Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: A proposal from an international consensus meeting","volume":"27","author":"Tsukasaki","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1046\/j.1365-2141.2001.02794.x","article-title":"Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: Response and outcome in 15 patients","volume":"113","author":"Matutes","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/sj.thj.6200195","article-title":"A prospective phase II clinical trial with the use of zidovudine and interferon-alpha in the acute and lymphoma forms of adult T-cell leukemia\/lymphoma","volume":"3","author":"Hermine","year":"2002","journal-title":"Hematol. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1200\/JCO.2010.28.0669","article-title":"Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia\/lymphoma showing improved survival in the leukemic subtypes","volume":"28","author":"Bazarbachi","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"58","DOI":"10.36401\/JIPO-22-1","article-title":"Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors in Oncology Clinical Trials: A review","volume":"5","author":"Feustel","year":"2022","journal-title":"J. Immunother. Precis. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/13543776.2023.2201436","article-title":"A patent review of PRMT5 inhibitors to treat cancer (2018\u2013present)","volume":"33","author":"Gao","year":"2023","journal-title":"Expert. Opin. Ther. Pat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11060-019-03274-0","article-title":"The protein arginine methyltransferase PRMT5 confers therapeutic resistance to mTOR inhibition in glioblastoma","volume":"145","author":"Holmes","year":"2019","journal-title":"J. Neurooncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.leukres.2006.08.001","article-title":"Longitudinal inhibition of PI3K\/Akt\/mTOR signaling by LY294002 and rapamycin induces growth arrest of adult T-cell leukemia cells","volume":"31","author":"Ikezoe","year":"2007","journal-title":"Leuk. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1182\/blood-2019-130797","article-title":"PRMT5 inhibition drives therapeutic vulnerability to BCL-2 inhibition with Venetoclax and provides rationale for combination therapy in mantle cell lymphoma","volume":"134","author":"Brown","year":"2019","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1021\/acs.jmedchem.1c01900","article-title":"Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5\u2022MTA Complex for the Treatment of MTAP-Deleted Cancers","volume":"65","author":"Smith","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6064","DOI":"10.1021\/acs.jmedchem.4c00133","article-title":"Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with MTAP-Deleted Cancers","volume":"67","author":"Cottrell","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1021\/acs.jmedchem.4c01998","article-title":"MTA-Cooperative PRMT5 Inhibitors: Mechanism Switching Through Structure-Based Design","volume":"68","author":"Cottrell","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6932","DOI":"10.1021\/acs.jmedchem.4c03121","article-title":"Discovery of AMG 193, an MTA-Cooperative PRMT5 Inhibitor for the Treatment of MTAP-Deleted Cancers","volume":"68","author":"Pettus","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/(SICI)1097-0215(19980105)75:1<51::AID-IJC9>3.0.CO;2-0","article-title":"The methylthioadenosine phosphorylase gene is frequently co-deleted with the p16INK4a gene in acute type adult T-cell leukemia","volume":"75","author":"Hori","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/sj.leu.2401771","article-title":"Detection of methylthioadenosine phosphorylase (MTAP) and p16 gene deletion in T cell acute lymphoblastic leukemia by real-time quantitative PCR assay","volume":"14","author":"Nishioka","year":"2000","journal-title":"Leukemia"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1126\/science.aad5214","article-title":"MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells","volume":"351","author":"Kryukov","year":"2016","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.aad5944","article-title":"Disordered methionine metabolism in MTAP\/CDKN2A-deleted cancers leads to dependence on PRMT5","volume":"351","author":"Mavrakis","year":"2016","journal-title":"Science"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/94\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:17:03Z","timestamp":1767968223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/94"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":91,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["v18010094"],"URL":"https:\/\/doi.org\/10.3390\/v18010094","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]}}}