{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:31:08Z","timestamp":1783603868818,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T00:00:00Z","timestamp":1566259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001171","name":"Cancer Institute NSW","doi-asserted-by":"publisher","award":["11\/TPG\/3\u201002"],"award-info":[{"award-number":["11\/TPG\/3\u201002"]}],"id":[{"id":"10.13039\/501100001171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001171","name":"Cancer Institute NSW","doi-asserted-by":"publisher","award":["2017\/TPG002"],"award-info":[{"award-number":["2017\/TPG002"]}],"id":[{"id":"10.13039\/501100001171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1134202"],"award-info":[{"award-number":["APP1134202"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["543727"],"award-info":[{"award-number":["543727"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"Antibody\u2010based therapy in acute myeloid leukemia (AML<\/jats:styled-content>) has been marred by significant hematologic toxicity due to targeting of both hematopoietic stem and progenitor cells (HSPC<\/jats:styled-content>s). Achieving greater success with therapeutic antibodies requires careful characterization of the potential target molecules on AML<\/jats:styled-content>. One potential target is CD<\/jats:styled-content>300f, which is an immunoregulatory molecule expressed predominantly on myeloid lineage cells. To confirm the value of CD<\/jats:styled-content>300f as a leukemic target, we showed that CD<\/jats:styled-content>300f antibodies bind to AML<\/jats:styled-content> from 85% of patient samples. While one CD<\/jats:styled-content>300f monoclonal antibody (mA<\/jats:styled-content>b) reportedly did not bind healthy hematopoietic stem cells, transcriptomic analysis found that CD<\/jats:styled-content>300f transcripts are expressed by healthy HSPC<\/jats:styled-content>. Several CD<\/jats:styled-content>300f protein isoforms exist as a result of alternative splicing. Importantly for antibody targeting, the extracellular region of CD<\/jats:styled-content>300f can be present with or without the exon 4\u2010encoded sequence. This results in CD<\/jats:styled-content>300f isoforms that are differentially bound by CD<\/jats:styled-content>300f\u2010specific antibodies. Furthermore, binding of one mA<\/jats:styled-content>b, DCR<\/jats:styled-content>\u20102, to CD<\/jats:styled-content>300f exposes a structural epitope recognized by a second CD<\/jats:styled-content>300f mA<\/jats:styled-content>b, UP<\/jats:styled-content>\u2010D2. Detailed analysis of publicly available transcriptomic data indicated that CD<\/jats:styled-content>34+<\/jats:sup> HSPC<\/jats:styled-content> expressed fewer CD<\/jats:styled-content>300f transcripts that lacked exon 4 compared to AML<\/jats:styled-content> with monocytic differentiation. Analysis of a small cohort of AML<\/jats:styled-content> cells revealed that the UP<\/jats:styled-content>\u2010D2 conformational binding site could be induced in cells from AML<\/jats:styled-content> patients with monocytic differentiation but not those from other AML<\/jats:styled-content> or HSPC<\/jats:styled-content>. This provides the opportunity to develop an antibody\u2010based strategy to target AML<\/jats:styled-content>s with monocytic differentiation but not healthy CD<\/jats:styled-content>34+<\/jats:sup> HSPC<\/jats:styled-content>s. This would be a major step forward in developing effective anti\u2010AML<\/jats:styled-content> therapeutic antibodies with reduced hematologic toxicity.<\/jats:p>","DOI":"10.1002\/1878-0261.12549","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T04:24:52Z","timestamp":1563942292000},"page":"2107-2120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CD<\/scp>300f epitopes are specific targets for acute myeloid leukemia with monocytic differentiation"],"prefix":"10.1002","volume":"13","author":[{"given":"Edward","family":"Abadir","sequence":"first","affiliation":[{"name":"Dendritic Cell Research ANZAC Research Institute Sydney Australia"},{"name":"Sydney Medical School University of Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin E.","family":"Gasiorowski","sequence":"additional","affiliation":[{"name":"Dendritic Cell Research ANZAC Research Institute Sydney Australia"},{"name":"Sydney Medical School University of Sydney Australia"},{"name":"Department of Haematology Concord Repatriation General Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitao","family":"Lai","sequence":"additional","affiliation":[{"name":"Sydney Medical School University of Sydney Australia"},{"name":"ANZAC Research Institute Sydney Australia"},{"name":"Northcott Neuroscience Laboratory ANZAC Research Institute Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Kupresanin","sequence":"additional","affiliation":[{"name":"Dendritic Cell Research ANZAC Research Institute Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina","family":"Romano","sequence":"additional","affiliation":[{"name":"Dendritic Cell Research ANZAC Research Institute Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo A.","family":"Silveira","sequence":"additional","affiliation":[{"name":"Dendritic Cell Research ANZAC Research Institute Sydney Australia"},{"name":"Sydney Medical School University of Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsun\u2010Ho","family":"Lo","sequence":"additional","affiliation":[{"name":"Dendritic Cell Research ANZAC Research Institute Sydney Australia"},{"name":"Sydney Medical School University of Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip D.","family":"Fromm","sequence":"additional","affiliation":[{"name":"Dendritic Cell Research ANZAC Research Institute Sydney Australia"},{"name":"Sydney Medical School University of Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina L.","family":"Kennerson","sequence":"additional","affiliation":[{"name":"Sydney Medical School University of Sydney Australia"},{"name":"Northcott Neuroscience Laboratory ANZAC Research Institute Sydney Australia"},{"name":"Molecular Medicine Laboratory Concord Repatriation General Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry J.","family":"Iland","sequence":"additional","affiliation":[{"name":"Sydney Medical School University of Sydney Australia"},{"name":"Institute of Haematology Royal Prince Alfred Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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