{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:14:25Z","timestamp":1790662465044,"version":"4.1.0"},"reference-count":47,"publisher":"American Association for Cancer Research (AACR)","issue":"11","funder":[{"DOI":"10.13039\/501100001659","name":"German research foundation","doi-asserted-by":"publisher","award":["PA 2541\/1-1"],"award-info":[{"award-number":["PA 2541\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R35 CA197594-01A1"],"award-info":[{"award-number":["R35 CA197594-01A1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01 CA108671"],"award-info":[{"award-number":["P01 CA108671"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","award":["DRG 22-17"],"award-info":[{"award-number":["DRG 22-17"]}],"id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K99 CA248460"],"award-info":[{"award-number":["K99 CA248460"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German research foundation","doi-asserted-by":"publisher","award":["PA 2541\/1-1"],"award-info":[{"award-number":["PA 2541\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>We investigated the role of PRMT5 in myeloproliferative neoplasm (MPN) pathogenesis and aimed to elucidate key PRMT5 targets contributing to MPN maintenance. PRMT5 is overexpressed in primary MPN cells, and PRMT5 inhibition potently reduced MPN cell proliferation ex vivo. PRMT5 inhibition was efficacious at reversing elevated hematocrit, leukocytosis, and splenomegaly in a model of JAK2V617F+ polycythemia vera and leukocyte and platelet counts, hepatosplenomegaly, and fibrosis in the MPLW515L model of myelofibrosis. Dual targeting of JAK and PRMT5 was superior to JAK or PRMT5 inhibitor monotherapy, further decreasing elevated counts and extramedullary hematopoiesis in vivo. PRMT5 inhibition reduced expression of E2F targets and altered the methylation status of E2F1 leading to attenuated DNA damage repair, cell-cycle arrest, and increased apoptosis. Our data link PRMT5 to E2F1 regulatory function and MPN cell survival and provide a strong mechanistic rationale for clinical trials of PRMT5 inhibitors in MPN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Expression of PRMT5 and E2F targets is increased in JAK2V617F+ MPN. Pharmacologic inhibition of PRMT5 alters the methylation status of E2F1 and shows efficacy in JAK2V617F\/MPLW515L MPN models and primary samples. PRMT5 represents a potential novel therapeutic target for MPN, which is now being clinically evaluated.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1611<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-20-0026","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T14:20:18Z","timestamp":1594822818000},"page":"1742-1757","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["PRMT5 Inhibition Modulates E2F1 Methylation and Gene-Regulatory Networks Leading to Therapeutic Efficacy in JAK2V617F-Mutant MPN"],"prefix":"10.1158","volume":"10","author":[{"given":"Friederike","family":"Pastore","sequence":"first","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Bhagwat","sequence":"additional","affiliation":[{"name":"3Prelude Therapeutics Inc., Wilmington, Delaware."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Pastore","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliaksandra","family":"Radzisheuskaya","sequence":"additional","affiliation":[{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"4Cell Biology Program, Memorial Sloan Kettering CancerCenter, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Karzai","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Krishnan","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Bowman","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8586-8500","authenticated-orcid":false,"given":"Wenbin","family":"Xiao","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"5Hematopathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D.","family":"Viny","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouar","family":"Zouak","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young C.","family":"Park","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith B.","family":"Cordner","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Braunstein","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2578-8872","authenticated-orcid":false,"given":"Jesper L.","family":"Maag","sequence":"additional","affiliation":[{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Grego","sequence":"additional","affiliation":[{"name":"3Prelude Therapeutics Inc., Wilmington, Delaware."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaanvi","family":"Mehta","sequence":"additional","affiliation":[{"name":"3Prelude Therapeutics Inc., Wilmington, Delaware."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"3Prelude Therapeutics Inc., Wilmington, Delaware."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Lin","sequence":"additional","affiliation":[{"name":"3Prelude Therapeutics Inc., Wilmington, Delaware."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin H.","family":"Durham","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Koche","sequence":"additional","affiliation":[{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0355-6368","authenticated-orcid":false,"given":"Raajit K.","family":"Rampal","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"6Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1975-6097","authenticated-orcid":false,"given":"Kristian","family":"Helin","sequence":"additional","affiliation":[{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"4Cell Biology Program, Memorial Sloan Kettering CancerCenter, New York, New York."},{"name":"7Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark."},{"name":"8The Novo Nordisk Foundation of Stem Cell Research (Danstem), University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Scherle","sequence":"additional","affiliation":[{"name":"3Prelude Therapeutics Inc., Wilmington, Delaware."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Vaddi","sequence":"additional","affiliation":[{"name":"3Prelude Therapeutics Inc., Wilmington, Delaware."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross L.","family":"Levine","sequence":"additional","affiliation":[{"name":"1Molecular Cancer Medicine Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"2Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"6Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York."},{"name":"9Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"2022060622132870300_bib1","doi-asserted-by":"crossref","first-page":"rs9","DOI":"10.1126\/scisignal.aaf7329","article-title":"Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells","volume":"9","author":"Larsen","year":"2016","journal-title":"Sci Signal"},{"key":"2022060622132870300_bib2","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":"2022060622132870300_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molcel.2008.12.013","article-title":"Protein arginine methylation in mammals: who, what, and why","volume":"33","author":"Bedford","year":"2009","journal-title":"Mol Cell"},{"key":"2022060622132870300_bib4","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.exphem.2016.03.009","article-title":"Arginine methyltransferases in normal and malignant hematopoiesis","volume":"44","author":"Greenblatt","year":"2016","journal-title":"Exp Hematol"},{"key":"2022060622132870300_bib5","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.bbagrm.2014.02.015","article-title":"Readers of histone methylarginine marks","volume":"1839","author":"Gayatri","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"2022060622132870300_bib6","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.dnarep.2013.04.006","article-title":"The role of arginine methylation in the DNA damage response","volume":"12","author":"Auclair","year":"2013","journal-title":"DNA Repair"},{"key":"2022060622132870300_bib7","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrc3409","article-title":"Protein arginine methyltransferases and cancer","volume":"13","author":"Yang","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"2022060622132870300_bib8","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":"2022060622132870300_bib9","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 Invest"},{"key":"2022060622132870300_bib10","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":"2022060622132870300_bib11","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":"2022060622132870300_bib12","doi-asserted-by":"crossref","first-page":"108790","DOI":"10.1016\/j.biopha.2019.108790","article-title":"Role of protein arginine methyltransferase 5 in human cancers","volume":"114","author":"Xiao","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"2022060622132870300_bib13","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.celrep.2016.03.043","article-title":"MTAP deletions in cancer create vulnerability to targeting of the MAT2A\/PRMT5\/RIOK1 axis","volume":"15","author":"Marjon","year":"2016","journal-title":"Cell Rep"},{"key":"2022060622132870300_bib14","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":"2022060622132870300_bib15","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/s41594-019-0313-z","article-title":"PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia","volume":"26","author":"Radzisheuskaya","year":"2019","journal-title":"Nat Struct Mol Biol"},{"key":"2022060622132870300_bib16","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ccell.2019.07.003","article-title":"Therapeutic targeting of RNA splicing catalysis through inhibition of protein arginine methylation","volume":"36","author":"Fong","year":"2019","journal-title":"Cancer Cell"},{"key":"2022060622132870300_bib17","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1182\/blood-2016-10-696005","article-title":"Myeloproliferative neoplasm stem cells","volume":"129","author":"Mead","year":"2017","journal-title":"Blood"},{"key":"2022060622132870300_bib18","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(05)71142-9","article-title":"Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders","volume":"365","author":"Baxter","year":"2005","journal-title":"Lancet"},{"key":"2022060622132870300_bib19","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/nature03546","article-title":"A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera","volume":"434","author":"James","year":"2005","journal-title":"Nature"},{"key":"2022060622132870300_bib20","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1182\/blood-2005-05-1898","article-title":"The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia","volume":"106","author":"Levine","year":"2005","journal-title":"Blood"},{"key":"2022060622132870300_bib21","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1056\/NEJMoa051113","article-title":"A gain-of-function mutation of JAK2 in myeloproliferative disorders","volume":"352","author":"Kralovics","year":"2005","journal-title":"N Engl J Med"},{"key":"2022060622132870300_bib22","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1038\/leu.2016.148","article-title":"Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis","volume":"30","author":"Harrison","year":"2016","journal-title":"Leukemia"},{"key":"2022060622132870300_bib23","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJMoa1110556","article-title":"JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis","volume":"366","author":"Harrison","year":"2012","journal-title":"N Engl J Med"},{"key":"2022060622132870300_bib24","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s13045-017-0527-7","article-title":"Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses","volume":"10","author":"Verstovsek","year":"2017","journal-title":"J Hematol Oncol"},{"key":"2022060622132870300_bib25","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1056\/NEJMoa1110557","article-title":"A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis","volume":"366","author":"Verstovsek","year":"2012","journal-title":"N Engl J Med"},{"key":"2022060622132870300_bib26","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1056\/NEJMoa0810069","article-title":"Mutation in TET2 in myeloid cancers","volume":"360","author":"Delhommeau","year":"2009","journal-title":"N Engl J Med"},{"key":"2022060622132870300_bib27","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ng.621","article-title":"Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders","volume":"42","author":"Ernst","year":"2010","journal-title":"Nat Genet"},{"key":"2022060622132870300_bib28","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1111\/j.1365-2141.2009.07697.x","article-title":"Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia","volume":"145","author":"Gelsi-Boyer","year":"2009","journal-title":"Br J Haematol"},{"key":"2022060622132870300_bib29","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ccr.2010.12.020","article-title":"JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation","volume":"19","author":"Liu","year":"2011","journal-title":"Cancer Cell"},{"key":"2022060622132870300_bib30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ccell.2015.06.006","article-title":"CHZ868, a type II JAK2 inhibitor, reverses type I JAK inhibitor persistence and demonstrates efficacy in myeloproliferative neoplasms","volume":"28","author":"Meyer","year":"2015","journal-title":"Cancer Cell"},{"key":"2022060622132870300_bib31","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nature11303","article-title":"Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy","volume":"489","author":"Koppikar","year":"2012","journal-title":"Nature"},{"key":"2022060622132870300_bib32","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1182\/blood-2014-02-554634","article-title":"Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis","volume":"123","author":"Rampal","year":"2014","journal-title":"Blood"},{"key":"2022060622132870300_bib33","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.ccr.2010.05.015","article-title":"Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells","volume":"17","author":"Mullally","year":"2010","journal-title":"Cancer Cell"},{"key":"2022060622132870300_bib34","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1158\/2159-8290.CD-14-0736","article-title":"JAK-STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response","volume":"5","author":"Kleppe","year":"2015","journal-title":"Cancer Discov"},{"key":"2022060622132870300_bib35","doi-asserted-by":"crossref","first-page":"e439","DOI":"10.1038\/bcj.2016.47","article-title":"A data-driven network model of primary myelofibrosis: transcriptional and post-transcriptional alterations in CD34+ cells","volume":"6","author":"Calura","year":"2016","journal-title":"Blood Cancer J"},{"key":"2022060622132870300_bib36","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/s41408-017-0010-2","article-title":"CALR mutational status identifies different disease subtypes of essential thrombocythemia showing distinct expression profiles","volume":"7","author":"Zini","year":"2017","journal-title":"Blood Cancer J"},{"key":"2022060622132870300_bib37","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.tibs.2004.06.006","article-title":"E2F target genes: unraveling the biology","volume":"29","author":"Bracken","year":"2004","journal-title":"Trends Biochem Sci"},{"key":"2022060622132870300_bib38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cytogfr.2013.01.004","article-title":"The role of cytokines in the initiation and progression of myelofibrosis","volume":"24","author":"Hasselbalch","year":"2013","journal-title":"Cytokine Growth Factor Rev"},{"key":"2022060622132870300_bib39","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.1182\/blood-2011-04-348144","article-title":"TNF\u03b1 facilitates clonal expansion of JAK2V617F positive cells in myeloproliferative neoplasms","volume":"118","author":"Fleischman","year":"2011","journal-title":"Blood"},{"key":"2022060622132870300_bib40","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1200\/JCO.2010.32.9490","article-title":"Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study","volume":"29","author":"Tefferi","year":"2011","journal-title":"J Clin Oncol"},{"key":"2022060622132870300_bib41","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1084\/jem.20110540","article-title":"A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2","volume":"209","author":"Kaufmann","year":"2012","journal-title":"J Exp Med"},{"key":"2022060622132870300_bib42","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1084\/jem.20160719","article-title":"Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression","volume":"214","author":"Kim","year":"2017","journal-title":"J Exp Med"},{"key":"2022060622132870300_bib43","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1038\/emboj.2012.17","article-title":"Arginine methylation controls growth regulation by E2F-1","volume":"31","author":"Cho","year":"2012","journal-title":"EMBO J"},{"key":"2022060622132870300_bib44","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1016\/j.celrep.2015.11.037","article-title":"RECQL5 suppresses oncogenic JAK2-induced replication stress and genomic instability","volume":"13","author":"Chen","year":"2015","journal-title":"Cell Rep"},{"key":"2022060622132870300_bib45","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1182\/blood-2017-05-784942","article-title":"Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in myeloproliferative neoplasms","volume":"130","author":"Nieborowska-Skorska","year":"2017","journal-title":"Blood"},{"key":"2022060622132870300_bib46","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1021\/acsmedchemlett.8b00014","article-title":"LLY-283, a potent and selective inhibitor of arginine methyltransferase 5, PRMT5, with antitumor activity","volume":"9","author":"Bonday","year":"2018","journal-title":"ACS Med Chem Lett"},{"key":"2022060622132870300_bib47","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1182\/blood-2009-04-218842","article-title":"Efficacy of the JAK2 inhibitor INCB16562 in a murine model of MPLW515L-induced thrombocytosis and myelofibrosis","volume":"115","author":"Koppikar","year":"2010","journal-title":"Blood"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/10\/11\/1742\/1816413\/1742.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/10\/11\/1742\/1816413\/1742.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T18:14:07Z","timestamp":1654539247000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/10\/11\/1742\/2347\/PRMT5-Inhibition-Modulates-E2F1-Methylation-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,1]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,2]]},"published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-20-0026","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.22535668.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22535665.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22535668","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22535665","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.6547909","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.6547909.v1","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,1]]}}}