{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:01:38Z","timestamp":1792612898226,"version":"4.5.0"},"reference-count":17,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a tumour target currently used for the development of novel therapeutic modalities, such as antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and others. Success of these new drugs depends on the selection of relevant indications based on ROR1 tumour prevalence, staining heterogeneity, and subcellular localization, among other parameters. We investigated ROR1 immunophenotype using validated antibody clones for immunohistochemistry (IHC) and flow cytometry (FC), analyzing 292 tumour specimens from 7 haematological malignancies and triple negative breast cancer (TNBC) as a reference solid tumour indication. ROR1 prevalence varied significantly across distinct tumour types, showing 100% of ROR1 positivity in all chronic lymphocytic leukaemia (n = 48) and hairy cell leukaemia (n = 14) specimens analyzed via FC with ranges between 1.1\u201399.8% and 0.8\u201362.1%, respectively. Samples analysed via IHC showed ROR1 membrane\/cytoplasmic positivity in 44% of mantle cell lymphoma tumour samples (n = 27; H-score range: 10\u2013285 in positive cases); 30% in TNBC (n = 46; H-score range: 1\u2013200); 15% in diffuse large B-cell lymphoma (n = 45; H-score: 40\u2013250); and 11% in follicular lymphoma (n = 34; H-score: 2\u2013300). Finally, all acute myeloid leukaemia (n = 52) and most T-cell non-Hodgkin lymphoma (n = 31\/32) tested samples were negative for ROR1 via IHC. In conclusion, ROR1 shows a heterogeneous tumour cell expression profile across multiple leukaemias and lymphomas, making it a tumour target that would require different patient selection strategies to develop novel therapeutic modalities.<\/jats:p>","DOI":"10.1371\/journal.pone.0313026","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T13:32:18Z","timestamp":1730727138000},"page":"e0313026","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tumour assessment of ROR1 levels in various adult leukaemia and lymphoma types"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-144X","authenticated-orcid":true,"given":"Manuel A.","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuntae","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Hauert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Ovadia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indu","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Waldmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yar\u00faa","family":"Jaimes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hytham","family":"Al-Masri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"pone.0313026.ref001","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s13238-014-0059-7","article-title":"ROR1, an embryonic protein with an emerging role in cancer biology","volume":"5","author":"N Borcherding","year":"2014","journal-title":"Protein Cell"},{"key":"pone.0313026.ref002","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.3390\/biomedicines10102559","article-title":"Pan-tissue and -cancer analysis of ROR1 and ROR2 transcript variants identify novel functional significance for an alternative splice variant of ROR1","volume":"10","author":"M John","year":"2022","journal-title":"Biomedicines"},{"key":"pone.0313026.ref003","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1158\/1078-0432.CCR-07-1823","article-title":"Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia","volume":"14","author":"S Baskar","year":"2008","journal-title":"Clin Cancer Res"},{"key":"pone.0313026.ref004","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1002\/ijc.23587","article-title":"Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy","volume":"123","author":"AH Daneshmanesh","year":"2008","journal-title":"Int J Cancer"},{"key":"pone.0313026.ref005","doi-asserted-by":"crossref","first-page":"843","DOI":"10.3109\/10428194.2012.731599","article-title":"Orphan receptor tyrosine kinases ROR1 and ROR2 in hematological malignancies","volume":"54","author":"AH Daneshmanesh","year":"2013","journal-title":"Leuk Lymphoma"},{"key":"pone.0313026.ref006","doi-asserted-by":"crossref","first-page":"4532","DOI":"10.1182\/blood-2010-05-283309","article-title":"The B cell tumour-associated antigen ROR1 can be targeted with T cells modified to express a ROR1- specific chimeric antigen receptor","volume":"116","author":"M Hudecek","year":"2010","journal-title":"Blood"},{"key":"pone.0313026.ref007","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1158\/1078-0432.CCR-16-2083","article-title":"Analysis of ROR1 protein expression in human cancer and normal tissues","volume":"23","author":"A Balakrishnan","year":"2017","journal-title":"Clin Cancer Res"},{"key":"pone.0313026.ref008","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.ajpath.2012.08.024","article-title":"The onco-embryonic antigen ROR1 is expressed by a variety of human cancers","volume":"181","author":"S Zhang","year":"2012","journal-title":"Am J Pathol"},{"key":"pone.0313026.ref009","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3390\/biomedicines8060170","article-title":"ROR1 is expressed in diffuse large B-cell lymphoma (DLBCL) and a small molecule inhibitor of ROR1 (KAN0441571C) induced apoptosis of lymphoma cells","volume":"8","author":"A Ghaderi","year":"2020","journal-title":"Biomedicines"},{"key":"pone.0313026.ref010","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1182\/blood.2021014760","article-title":"ROR1: an orphan becomes apparent","volume":"140","author":"TJ Kipps","year":"2022","journal-title":"Blood"},{"key":"pone.0313026.ref011","first-page":"205","article-title":"Up-date on hairy cell leukemia","volume":"16","author":"RJ Kreitman","year":"2018","journal-title":"Clin Adv Hematol Oncol"},{"key":"pone.0313026.ref012","doi-asserted-by":"crossref","first-page":"e0196464","DOI":"10.1371\/journal.pone.0196464","article-title":"PD-L1 immunostaining scoring for non-small cell lung cancer based onimmunosurveillance parameters","volume":"13","author":"MA Silva","year":"2018","journal-title":"PLOS ONE"},{"key":"pone.0313026.ref013","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/cjp2.152","article-title":"Biomarker recommendation for PD-1\/PD-L1 immunotherapy development in pediatric cancer based on digital image analysis of PD-L1 and immune cells","volume":"6","author":"MA Silva","year":"2020","journal-title":"J Pathol Clin Res"},{"key":"pone.0313026.ref014","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.cll.2017.07.001","article-title":"Flow cytometry of B-cell neoplasms","volume":"37","author":"SH Kroft","year":"2017","journal-title":"Clin Lab Med"},{"key":"pone.0313026.ref015","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/cyto.b.21854","article-title":"Common flow cytometry pitfalls in diagnostic hematopathology","volume":"96B","author":"S Cherian","year":"2019","journal-title":"Cytometry"},{"key":"pone.0313026.ref016","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1182\/blood-2016-04-712562","article-title":"High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia","volume":"128","author":"B Cui","year":"2016","journal-title":"Blood"},{"key":"pone.0313026.ref017","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/cyto.b.22157","article-title":"ROR1 expression in mature B lymphoid neoplasms by flow cytometry","volume":"106","author":"F Arandas de Sousa","year":"2024","journal-title":"Cytometry B Clin Cytom"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T13:32:24Z","timestamp":1730727144000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313026"}},"subtitle":[],"editor":[{"given":"Jian","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,4]]},"references-count":17,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0313026","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,4]]}}}