{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:37:46Z","timestamp":1787776666943,"version":"build-2784847793"},"reference-count":54,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Midwest Athletes Against Childhood Cancer (MACC) Fund"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31-HL140914"],"award-info":[{"award-number":["F31-HL140914"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL126785"],"award-info":[{"award-number":["R01-HL126785"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL134010"],"award-info":[{"award-number":["R01-HL134010"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,7,2]]},"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface <jats:italic>N<\/jats:italic>-glycoproteome of MM cell lines. Next, we developed targeted MS assays, and applied these to cell lines and primary patient samples to refine the list of candidate tumor markers. Candidates of interest detected by MS on MM patient samples were further validated using flow cytometry (FCM).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 696\u2009MM cell surface <jats:italic>N<\/jats:italic>-glycoproteins by CSC, and developed 73 targeted MS detection assays. MS-based validation using primary specimens detected 30 proteins with significantly higher abundance in patient MM cells than controls. Nine of these proteins were identified as potential immunotherapeutic targets, including five that were validated by FCM, confirming their expression on the cell surface of primary MM patient cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This MM surface <jats:italic>N<\/jats:italic>-glycoproteome will be a valuable resource in the development of biomarkers and therapeutics. Further, we anticipate that our targeted MS assays will have clinical benefit for the diagnosis, stratification, and treatment of MM patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-000915","type":"journal-article","created":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T21:00:40Z","timestamp":1596920440000},"page":"e000915","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Discovery and validation of surface <i>N<\/i>-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct03081910","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03403725","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02040506","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03149549","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Robyn A A","family":"Oldham","sequence":"first","affiliation":[{"name":"Medical Biophysics, University of Toronto Faculty of Medicine, Toronto, Ontario, Canada"},{"name":"Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary L","family":"Faber","sequence":"additional","affiliation":[{"name":"Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore R","family":"Keppel","sequence":"additional","affiliation":[{"name":"Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"},{"name":"Center for Biomedical Mass Spectrometry Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda R","family":"Buchberger","sequence":"additional","affiliation":[{"name":"Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"},{"name":"Center for Biomedical Mass Spectrometry Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Waas","sequence":"additional","affiliation":[{"name":"Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"},{"name":"Center for Biomedical Mass Spectrometry Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parameswaran","family":"Hari","sequence":"additional","affiliation":[{"name":"Division of Hematology Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah L","family":"Gundry","sequence":"additional","affiliation":[{"name":"Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"},{"name":"Center for Biomedical Mass Spectrometry Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A","family":"Medin","sequence":"additional","affiliation":[{"name":"Medical Biophysics, University of Toronto Faculty of Medicine, Toronto, Ontario, Canada"},{"name":"Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"},{"name":"Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"2025100302482606000_8.2.e000915.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.12.015"},{"key":"2025100302482606000_8.2.e000915.2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0866"},{"key":"2025100302482606000_8.2.e000915.3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/cyto.b.21265","article-title":"Immunophenotype of normal vs. myeloma plasma cells: toward antibody panel specifications for MRD detection in multiple myeloma","volume":"90","author":"Flores-Montero","year":"2016","journal-title":"Cytometry B Clin Cytom"},{"key":"2025100302482606000_8.2.e000915.4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.trsl.2018.05.003","article-title":"Novel biomarkers in multiple myeloma","volume":"201","author":"Levin","year":"2018","journal-title":"Transl Res"},{"key":"2025100302482606000_8.2.e000915.5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-506170"},{"key":"2025100302482606000_8.2.e000915.6","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24402"},{"key":"2025100302482606000_8.2.e000915.7","unstructured":"Cancer STAT facts: myeloma: National cancer Institute surveillance, epidemiology, and end results program, 2014. 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