{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:00:07Z","timestamp":1793660407085,"version":"4.5.1"},"reference-count":12,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mogamulizumab is a humanized anti\u2013CC chemokine receptor 4 (CCR4) antibody approved for the treatment of mycosis fungoides and S\u00e9zary syndrome. Despite almost universal expression of CCR4 in these diseases, most patients eventually develop resistance to mogamulizumab. We tested whether resistance to mogamulizumab is associated with loss of CCR4 expression. We identified 17 patients with mycosis fungoides or S\u00e9zary syndrome who either were intrinsically resistant or acquired resistance to mogamulizumab. Low expression of CCR4 by immunohistochemistry or flow cytometry was found in 65% of patients. Novel emergent CCR4 mutations targeting the N-terminal and transmembrane domains were found in 3 patients after disease progression. Emerging CCR4 copy number loss was detected in 2 patients with CCR4 mutations. Acquisition of CCR4 genomic alterations corresponded with loss of CCR4 antigen expression. We also report on outcomes of 3 cutaneous T-cell lymphoma (CTCL) patients with gain-of-function CCR4 mutations treated with mogamulizumab. Our study indicates that resistance to mogamulizumab in CTCL frequently involves loss of CCR4 expression and emergence of CCR4 genomic alterations. This finding has implications for management and monitoring of CTCL patients on mogamulizumab and development of future CCR4-directed therapies.<\/jats:p>","DOI":"10.1182\/blood.2021014468","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T15:02:50Z","timestamp":1650294170000},"page":"3732-3736","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["Resistance to mogamulizumab is associated with loss of CCR4 in cutaneous T-cell lymphoma"],"prefix":"10.1182","volume":"139","author":[{"given":"Sara","family":"Beygi","sequence":"first","affiliation":[{"name":"1Division of Oncology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2692-3906","authenticated-orcid":false,"given":"George E.","family":"Duran","sequence":"additional","affiliation":[{"name":"1Division of Oncology, Department of Medicine,"},{"name":"2Department of Dermatology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0428-0199","authenticated-orcid":false,"given":"Sebastian","family":"Fernandez-Pol","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Stanford University, Stanford, CA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain H.","family":"Rook","sequence":"additional","affiliation":[{"name":"4Department of Dermatology, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2686-5873","authenticated-orcid":false,"given":"Youn H.","family":"Kim","sequence":"additional","affiliation":[{"name":"1Division of Oncology, Department of Medicine,"},{"name":"2Department of Dermatology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9061-7351","authenticated-orcid":false,"given":"Michael S.","family":"Khodadoust","sequence":"additional","affiliation":[{"name":"1Division of Oncology, Department of Medicine,"},{"name":"2Department of Dermatology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"6","key":"2022063015215058200_B1","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1046\/j.1523-1747.2002.19610.x","article-title":"Increased CCR4 expression in cutaneous T cell lymphoma","volume":"119","author":"Ferenczi","year":"2002","journal-title":"J Invest Dermatol."},{"issue":"1","key":"2022063015215058200_B2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/intimm\/dxu079","article-title":"CCR4 and its ligands: from bench to bedside","volume":"27","author":"Yoshie","year":"2015","journal-title":"Int 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Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer","volume":"29","author":"Olsen","year":"2011","journal-title":"J Clin Oncol."},{"issue":"13","key":"2022063015215058200_B6","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1084\/jem.20140987","article-title":"Gain-of-function CCR4 mutations in adult T cell leukemia\/lymphoma","volume":"211","author":"Nakagawa","year":"2014","journal-title":"J Exp Med."},{"issue":"12","key":"2022063015215058200_B7","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1038\/ng.3444","article-title":"Genomic profiling of S\u00e9zary syndrome identifies alterations of key T cell signaling and differentiation genes","volume":"47","author":"Wang","year":"2015","journal-title":"Nat Genet."},{"issue":"3","key":"2022063015215058200_B8","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1182\/bloodadvances.2020002371","article-title":"Pembrolizumab in mycosis fungoides with PD-L1 structural variants","volume":"5","author":"Beygi","year":"2021","journal-title":"Blood Adv."},{"issue":"1","key":"2022063015215058200_B9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1200\/JCO.19.01056","article-title":"Pembrolizumab in relapsed and refractory mycosis fungoides and S\u00e9zary syndrome: a multicenter phase II study","volume":"38","author":"Khodadoust","year":"2020","journal-title":"J Clinl Oncol."},{"issue":"4","key":"2022063015215058200_B10","doi-asserted-by":"crossref","first-page":"e1004873","DOI":"10.1371\/journal.pcbi.1004873","article-title":"CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing","volume":"12","author":"Talevich","year":"2016","journal-title":"PLOS Comput Biol."},{"issue":"1","key":"2022063015215058200_B11","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/cjp2.180","article-title":"Immunohistochemistry for CCR4 C-terminus predicts CCR4 mutations and mogamulizumab efficacy in adult T-cell leukemia\/lymphoma","volume":"7","author":"Fujii","year":"2021","journal-title":"J Pathol Clin Res."},{"issue":"7","key":"2022063015215058200_B12","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1182\/blood-2018-02-835991","article-title":"CCR4 mutations associated with superior outcome of adult T-cell leukemia\/lymphoma under mogamulizumab treatment","volume":"132","author":"Sakamoto","year":"2018","journal-title":"Blood."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/26\/3732\/1904555\/bloodbld2021014468.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/26\/3732\/1904555\/bloodbld2021014468.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T11:22:09Z","timestamp":1656588129000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/139\/26\/3732\/484969\/Resistance-to-mogamulizumab-is-associated-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":12,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2022,6,30]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2021014468","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742002738.793592707","asserted-by":"object"}]},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}