{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:05:54Z","timestamp":1793739954931,"version":"4.6.1"},"reference-count":71,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T00:00:00Z","timestamp":1534723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"miRagen Therapeutics, Inc"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    miR\u2010155, a microRNA associated with poor prognosis in lymphoma and leukaemia, has been implicated in the progression of mycosis fungoides (\n                    <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\n                    ), the most common form of cutaneous T\u2010cell lymphoma (CTCL). In this study, we developed and tested cobomarsen (MRG\u2010106), a locked nucleic acid\u2010modified oligonucleotide inhibitor of miR\u2010155. In\n                    <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\n                    and human lymphotropic virus type 1 (HTLV\u20101+) CTCL cell lines\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    , inhibition of miR\u2010155 with cobomarsen de\u2010repressed direct miR\u2010155 targets, decreased expression of multiple gene pathways associated with cell survival, reduced survival signalling, decreased cell proliferation and activated apoptosis. We identified a set of genes that are significantly regulated by cobomarsen, including direct and downstream targets of miR\u2010155. Using clinical biopsies from\n                    <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\n                    patients, we demonstrated that expression of these pharmacodynamic biomarkers is dysregulated in\n                    <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\n                    and associated with miR\u2010155 expression level and\n                    <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\n                    lesion severity. Further, we demonstrated that miR\u2010155 simultaneously regulates multiple parallel survival pathways (including JAK\/STAT, MAPK\/ERK and PI3K\/AKT) previously associated with the pathogenesis of\n                    <jats:styled-content style=\"fixed-case\">MF<\/jats:styled-content>\n                    , and that these survival pathways are inhibited by cobomarsen\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    . A first\u2010in\u2010human phase 1 clinical trial of cobomarsen in patients with CTCL is currently underway, in which the panel of proposed biomarkers will be leveraged to assess pharmacodynamic response to cobomarsen therapy.\n                  <\/jats:p>","DOI":"10.1111\/bjh.15547","type":"journal-article","created":{"date-parts":[[2018,8,20]],"date-time":"2018-08-20T14:57:18Z","timestamp":1534777038000},"page":"428-444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":329,"title":["Cobomarsen, an oligonucleotide inhibitor of miR\u2010155, co\u2010ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T\u2010cell lymphoma"],"prefix":"10.1111","volume":"183","author":[{"given":"Anita G.","family":"Seto","sequence":"first","affiliation":[{"name":"miRagen Therapeutics, Inc. Boulder CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Beatty","sequence":"additional","affiliation":[{"name":"miRagen Therapeutics, Inc. Boulder CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Lynch","sequence":"additional","affiliation":[{"name":"miRagen Therapeutics, Inc. Boulder CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hermreck","sequence":"additional","affiliation":[{"name":"miRagen Therapeutics, Inc. Boulder CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tetzlaff","sequence":"additional","affiliation":[{"name":"Section\u00a0of Dermatopathology Department of Pathology Department of Translational and Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Duvic","sequence":"additional","affiliation":[{"name":"Department of Dermatology The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3786-7391","authenticated-orcid":false,"given":"Aimee L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"miRagen Therapeutics, Inc. Boulder CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.12.10.17681"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201516109"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-256719"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811073106"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602266103"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12578"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500613102"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.03.014"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5259-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.231"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0010013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.013"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2000.20370"},{"key":"e_1_2_8_16_1","first-page":"878","article-title":"HCV infection and miravirsen","volume":"369","author":"Janssen H.L.","year":"2013","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2011.02.003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.117"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1825"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.24987"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12162"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.12.035"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3932"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02005-06"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2879"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.25550"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4161\/15384101.2014.947759"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-3322"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1306618"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjr007"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10669.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-015-9897-8"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.815352"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10316"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12161"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15422"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2011.32"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.305"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21619"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-544197"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072108"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902636106"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900028"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.12.7415"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2017.1378096"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.9.2778"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.481"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-358382"},{"key":"e_1_2_8_50_1","first-page":"7207","article-title":"MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T\u2010cell lymphoma","volume":"34","author":"Ralfkiaer U.","year":"2014","journal-title":"Anticancer Research"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0660-z"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204382"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.487"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-017-0177-y"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-061507"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01804-07"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20112092"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2536"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0000060"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101795108"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1089\/107999004322917034"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002472107"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21305"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00510.x"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3444"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt242"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2014.15.18.7547"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-222794"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-3156-1"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430303"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708218200"},{"key":"e_1_2_8_72_1","first-page":"1234","article-title":"Induction of apoptosis by bexarotene in cutaneous T\u2010cell lymphoma cells: relevance to mechanism of therapeutic action","volume":"8","author":"Zhang C.","year":"2002","journal-title":"Clinical Cancer Research"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.15547","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.15547","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T14:26:41Z","timestamp":1694788001000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.15547"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,20]]},"references-count":71,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/bjh.15547"],"URL":"https:\/\/doi.org\/10.1111\/bjh.15547","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,20]]},"assertion":[{"value":"2018-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}