{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:37:39Z","timestamp":1787668659477,"version":"build-2736575974"},"reference-count":102,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Treatment of relapsed or refractory acute myeloid leukaemia (AML) has remained a significant challenge, with limited available targeted immunotherapies. CD123, or the interleukin\u20103 (IL\u20103) receptor, has long been known as a potential target expressed on AML blasts, and a range of different approaches to targeting CD123 have been trialled with variable anti\u2010tumour responses and toxicities observed. Here, we review the clinical outcomes of these therapies, including monoclonal antibodies and antibody\u2010drug conjugates, as well as bispecific T\u2010cell engager molecules and chimeric antigen receptor (CAR) T cells. We discuss the potential reasons for therapy\u2010associated toxicity and limited efficacy, including differential antigen expression, the AML microenvironment and patient\u2010derived T\u2010cell fitness. To address these challenges, we highlight novel approaches to CD123 targeting currently in preclinical development. Promising new strategies include combination therapies that target CD123 and other known AML\u2010associated antigens such as CD33 or CLL\u20101, NK\u2010cell\u2010based cell therapies, and bispecific\u2010secreting T cells.<\/jats:p>","DOI":"10.1111\/bjh.70019","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T01:15:32Z","timestamp":1753406132000},"page":"1178-1191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<scp>CD123<\/scp>\u2010targeting immunotherapeutic approaches in acute myeloid leukaemia"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1414-290X","authenticated-orcid":false,"given":"Alexandra","family":"Dreyzin","sequence":"first","affiliation":[{"name":"Center for Cellular Engineering National Institutes of Health Clinical Center  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-1109","authenticated-orcid":false,"given":"Noa G.","family":"Holtzman","sequence":"additional","affiliation":[{"name":"National Cancer Institute National Institutes of Health  Bethesda Maryland USA"},{"name":"Division of Transplantation and Cellular Therapy, Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Challice L.","family":"Bonifant","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401903"},{"key":"e_1_2_10_3_1","first-page":"1261","article-title":"Interleukin\u20103 receptor alpha chain (CD123) is widely expressed in hematologic malignancies","volume":"86","author":"Mu\u00f1oz L","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2020.106477"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.04.018"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01595"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0852"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.047894"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21745"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403458"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-023-03612-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07491.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-309179"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113087"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-014-1590-2"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2020.05.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2018.09.005"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0218674"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/2050-7771-2-4"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.11137"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.118518"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.1349.1349"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V120.21.1524.1524"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.2316.2316"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa5693"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190410001663572"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-004-0643-4"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0773-5"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190701799035"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011721"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00674-5"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-158030"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007732"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13164113"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010956"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-208684"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13467"},{"key":"e_1_2_10_38_1","article-title":"Treating relapsed\/refractory (RR) AML with biodegradable anti\u2010CD123 CAR modified T cells","volume":"130","author":"Cummins KD","year":"2017","journal-title":"Blood"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6074.TUMIMM18-PR14"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03271-5"},{"issue":"9","key":"e_1_2_10_41_1","first-page":"2275","article-title":"Relapsed pediatric acute myeloid leukaemia: state\u2010of\u2010the\u2010art in 2023","volume":"108","author":"Egan G","year":"2023","journal-title":"Haematologica"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-208795"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-168877"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-169928"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0645-z"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.120.120"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1815105"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2329"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.205252"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018017517"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-013-1157-8"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02340"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-575704"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz0463"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-163075"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-199211"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01145-x"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-194356"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-173162"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-021-00294-9"},{"key":"e_1_2_10_61_1","article-title":"Pre\u2010clinical development of a novel CD3\u2010CD123 bispecific T\u2010cell engager using cross\u2010over dual\u2010variable domain (CODV) format for acute myeloid leukemia (AML) treatment","volume":"10","author":"Bonnevaux H","year":"2021","journal-title":"Onco Targets Ther"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00335-7"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-166385"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.120974"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI159579"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.3778.3778"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-170201"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(24)00273-4"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2019.05.003"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009759"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01358"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15456"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.188193"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16233974"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2001.01692.x"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-201034"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01350-x"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.214"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-734798"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.764698"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01959-0"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1061-7"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0010-1"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001797"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1314"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-184918"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad5222"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30842"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.03279"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015795"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01708-z"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2023.100751"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.22074\/cellj.2021.7314"},{"key":"e_1_2_10_94_1","article-title":"CAR\u2010T cells dual\u2010target CD123 and NKG2DLs to eradicate AML cells and selectively target immunosuppressive cells","volume":"12","author":"Jin X","year":"2023","journal-title":"Onco Targets Ther"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-01905-0"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.116"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.156"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2018.07.005"},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.880108"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279301"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01376-3"},{"key":"e_1_2_10_102_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010763"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003894"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T10:09:40Z","timestamp":1760090980000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.70019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":102,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/bjh.70019"],"URL":"https:\/\/doi.org\/10.1111\/bjh.70019","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]},"assertion":[{"value":"2025-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}