{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:53:32Z","timestamp":1790657612984,"version":"4.1.0"},"reference-count":129,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In spite of consistent progress at the level of basic research and of clinical treatment, acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric patients. To improve the outcomes of these patients, it is necessary to identify new therapeutic targets. IL3RA (CD123, alpha subunit of the interleukin 3 receptor) is a cell membrane protein overexpressed in several hematologic malignancies, including AML blastic plasmocytoid dendritic cell neoplasms (BPDCN). Given the higher expression of CD123 on leukemic cells compared to normal hematopoietic cells and its low\/absent expression on normal hematopoietic stem cells, it appears as a suitable and attractive target for therapy. Various drugs targeting CD123 have been developed and evaluated at clinical level: interleukin-3 conjugated with diphtheria toxin; naked neutralizing anti-CD123 antibodies; drug\u2013antibody conjugates; bispecific antibodies targeting both CD123 and CD3; and chimeric antigen receptor (CAR) T cells engineered to target CD123. Some of these agents have shown promising results at the clinical level, including tagraxofusp (CD123 conjugated with diphtheria toxin) for the treatment of BPDCN and IMGN632 (anti-CD123 drug-conjugate), and flotetuzumab (bispecific anti-CD123 and anti-CD3 monoclonal antibody) for the treatment of AML. However, the therapeutic efficacy of CD123-targeting treatments is still unsatisfactory and must be improved through new therapeutic strategies and combined treatments with other antileukemic drugs.<\/jats:p>","DOI":"10.3390\/ijms24032718","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:52:02Z","timestamp":1675219922000},"page":"2718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["CD123 a Therapeutic Target for Acute Myeloid Leukemia and Blastic Plasmocytoid Dendritic Neoplasm"],"prefix":"10.3390","volume":"24","author":[{"given":"Elvira","family":"Pelosi","sequence":"first","affiliation":[{"name":"Department of Oncology, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germana","family":"Castelli","sequence":"additional","affiliation":[{"name":"Department of Oncology, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-8942","authenticated-orcid":false,"given":"Ugo","family":"Testa","sequence":"additional","affiliation":[{"name":"Department of Oncology, Istituto Superiore di Sanit\u00e0, Viale Regina Elena 299, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref_1","unstructured":"Swerdlow, S.H., Campo, E., and Harris, N.L. (2008). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel on the behalf of the ENL","volume":"140","author":"Dohner","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research, Ley, T.J., Miller, C., Ding, L., Raphael, B.J., Mingall, A.J., Robertson, A.G., Hoadley, A.S.K., Triche, T.J., and Laird, P.W. (2013). Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med., 368, 20959\u201322074.","DOI":"10.1056\/NEJMoa1301689"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/leu.2013.236","article-title":"Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia","volume":"28","author":"Hou","year":"2014","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic classification and prognosis in acute myeloid leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1200\/JCO.2016.71.2208","article-title":"Genomics of acute myeloid leukemia diagnosis and pathways","volume":"35","author":"Bullinger","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/MOH.0000000000000567","article-title":"Driver mutations in acute myeloid leukemia","volume":"27","author":"Kishtagari","year":"2020","journal-title":"Curr. Opin. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shomony, S., Stahl, M., and Stone, R.M. (2023). Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am. J. Hematol., in press.","DOI":"10.1002\/ajh.26822"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1200\/EDBK_349605","article-title":"Contemporary approach to acute myeloid leukemia therapy in 2022","volume":"42","author":"Roloff","year":"2022","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/PPO.0000000000000577","article-title":"Monoclonal antibodies in acute myeloid leukemia-are we there yet?","volume":"28","author":"Abaza","year":"2022","journal-title":"Cancer J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1182\/blood.V88.9.3391.bloodjournal8893391","article-title":"Expression of growth factor receptors in unilineage differentiation culture of purified hematopoietic progenitors","volume":"88","author":"Testa","year":"1996","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2050-7771-2-4","article-title":"CD123 is a membrane biomarker and a therapeutic target in hematologic malignancies","volume":"2","author":"Testa","year":"2014","journal-title":"Biomark. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1038\/sj.leu.2401903","article-title":"The interleukin-3 receptor alpha is a unique marker for human acute myelogenous leukemia stem cells","volume":"14","author":"Jordan","year":"2000","journal-title":"Leukemia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1182\/blood-2002-03-0852","article-title":"Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity and poor prognosis","volume":"100","author":"Testa","year":"2002","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1182\/bloodadvances.2016002931","article-title":"High CD123 levels enhance proliferation is response to IL-3, but reduce chemotaxis by downregulating CXCR4 expression","volume":"1","author":"Wittwer","year":"2017","journal-title":"Blood Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s12185-019-02616-y","article-title":"Impact of CD123 expression, analyzed by immunohistochemistry, on clinical outcomes in patients with acute myeloid leukemia","volume":"109","author":"Arai","year":"2019","journal-title":"Int. J. Hematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/sj.leu.2403224","article-title":"Interleukin-3 receptor in acute leukemia","volume":"18","author":"Testa","year":"2004","journal-title":"Leukemia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/j.1365-2141.2008.07491.x","article-title":"Interleukin (IL)-3\/granulocyte macrophage-colony stimulating factor \/IL-5 receptor alpha and beta chains are preferentially expressed in acute myeloid leukemias with mutated FMS-related tyrosine 3 kinase receptor","volume":"144","author":"Riccioni","year":"2009","journal-title":"Br. J. Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1365-2141.2011.08577.x","article-title":"Immunophenotypic features of acute myeloid leukemia patients exhibiting high Flt3 expression not associated with mutations","volume":"153","author":"Riccioni","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1097\/PAI.0b013e318261a342","article-title":"CD123 immunohistochemical expression in acute myeloid leukemia is associated with underlying FLT3-ITD and NPM1 mutations","volume":"21","author":"Pillai","year":"2013","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_21","first-page":"142","article-title":"CD123 expression levels in 846 acute leukemia patients based on standardized immunophenotyping","volume":"96","author":"Brass","year":"2019","journal-title":"Cytom. Part B Clin. Cytom."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Perriello, V.M., Gionfriddo, I., Rossi, R., Milano, F., Mezzasoma, F., Marra, A., Spinelli, O., Rambaldi, A., Annibali, O., and Avvisati, G. (2021). CD123 is consistently expressed on NPM1-mutated AML cells. Cancers, 13.","DOI":"10.3390\/cancers13030496"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1080\/10428194.2021.1927018","article-title":"Quantitative analyses of CD7, CD33, CD34, CD56 and CD123 within FLT3-ITD\/NPM1-MUT myeloblastic\/monocytic bulk AML blastic populations","volume":"62","author":"Soare","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13045-016-0292-z","article-title":"Immunoprofiling of leukemic stem cells CD34+\/CD38\u2212\/CD123+ delineate FLT3\/ITD-positive clones","volume":"9","author":"Gillis","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1158\/1078-0432.CCR-14-3186","article-title":"A leukemia-associated CD34\/CD123\/CD25\/CD99+ immunophenotype identifies FLT3-mutated clones in acute myeloid leukemia","volume":"21","author":"Angelini","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41408-020-00352-9","article-title":"Characterization of FLT3-ITDmut acute myeloid leukemia: Molecular profiling of leukemic precursor cells","volume":"10","author":"Travaglini","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1200\/JCO.21.01595","article-title":"CD123 expression is associated with high-risk disease characteristics in childhood acute myeloid leukemia: A report from the children\u2019s oncology group","volume":"40","author":"Lamble","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1182\/blood.V98.8.2301","article-title":"Nuclear factor B is constitutively activated in primitive acute human acute myelogenous leukemia cells","volume":"98","author":"Guzman","year":"2011","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.3324\/haematol.2011.047894","article-title":"High levels of CD34+CD38low\/CD123+ blasts are predictive of an adverse outcome in acute myeloid leukemia","volume":"96","author":"Vergez","year":"2011","journal-title":"Haematologica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.1182\/bloodadvances.2020001742","article-title":"Delineation of target expression profiles in CD34+CD38\u2212 and CD34+CD38+ stem and progenitor cells in AML and CML","volume":"4","author":"Hermann","year":"2020","journal-title":"Blood Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41408-022-00712-7","article-title":"Phenotypically-defined stages of leukemic arrest predict main driver mutations subgroups, and oucome in acute myeloid leukemia","volume":"12","author":"Vergez","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41375-018-0180-3","article-title":"Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML","volume":"33","author":"Haubner","year":"2019","journal-title":"Leukemia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1182\/bloodadvances.2021005018","article-title":"CombiFlow: Combinatorial AML-specific plasma membrane expression profiles allow longitudinal trcking of clones","volume":"6","author":"Houtsma","year":"2022","journal-title":"Blood Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3233\/CBM-201519","article-title":"Clinical value of CD25\/CD123 co-expression in acute myeloid leukemia patients","volume":"29","author":"Aref","year":"2020","journal-title":"Cancer Biomark."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Allen, C., Zeidan, A.M., and Bewersdorf, J.P. (2021). BiTEs, DARTs, BiKEs and TriKEs\u2014Are antibody-based therapies changing the future treatments of AML?. Life, 11.","DOI":"10.3390\/life11060465"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/sj.leu.2401743","article-title":"Diphteria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias","volume":"14","author":"Frankel","year":"2000","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.cell.2017.01.016","article-title":"The principles of engineering immune cells to treat cancer","volume":"168","author":"Lim","year":"2017","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1080\/10428190410001663572","article-title":"Toxicology and pharmacokinetics of DT388IL3, a fusion protein consisting of a truncated diphteria toxin (DT388) linked to human interleukin 3 (IL3) in cynomolgous monkeys","volume":"45","author":"Cohen","year":"2004","journal-title":"Leuk. Lymphoma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00262-004-0643-4","article-title":"Safety evaluation of DT388IL3, a diphteria toxin\/interleukin 3 fusion protein, in cynomolgus monkey","volume":"54","author":"Cohen","year":"2005","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1182\/blood-2005-02-0540","article-title":"Diphteria toxin fused to variant human interleukin-3 induces cytotoxicity of blasts from patients with acute myeloid leukemia according to the level of interleukin-3 receptor expression","volume":"106","author":"Testa","year":"2005","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.1182\/blood-2006-04-013813","article-title":"Expression of interleukin-3 receptor subunits on defined subpopulations of acute myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin-3 fusion protein against malignant progenitors that engraft in immunodeficient mice","volume":"108","author":"Yalcintepe","year":"2006","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/1078-0432.CCR-05-2070","article-title":"Variant diphtheria toxin-interleukin-3 fusion proteins with increased receptor affinity have enhanced cytotoxicity against acute myeloid leukemia progenitors","volume":"12","author":"Hogge","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pemmaraju, N., Kantarjian, H.M., Sweet, K.L., Wang, E.S., Senapati, J., Wilson, N.R., Konopleva, M.Y., Frankel, A.E., Gupta, V., and Mesa, R.A. (2022). North American blastic plasmocytoid dendritic cell neopleasm consortium: Position on standards of care and areas of need. Blood, 11\u201318.","DOI":"10.1182\/blood.2022017865"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1182\/blood-2014-04-566737","article-title":"Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients","volume":"124","author":"Frankel","year":"2014","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1056\/NEJMoa1815105","article-title":"Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm","volume":"380","author":"Pemmaraju","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13045-018-0604-6","article-title":"First pediatric experience of SL-401, a CD123-targeted tehrapy, in patients with blastic plasmocytoid dendritic cell neoplasm: Report of three cases","volume":"11","author":"Sun","year":"2018","journal-title":"J. Hemtol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S244","DOI":"10.1016\/S2152-2650(22)01284-8","article-title":"AML-392 treatment of blastic plasmocytoid dendritic cell neoplasm in pedaitric patients with tagraxofusp, a CD123-targeted therapy","volume":"22","author":"Pemmaraju","year":"2022","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1200\/JCO.22.00034","article-title":"Long-term benefit of tagraxofusp for patients with blastic plasmocytoid dendritic cell neoplasm","volume":"40","author":"Pemmaraju","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S254","DOI":"10.1016\/S2152-2650(22)01301-5","article-title":"AML-465 tagraxofusp, an anti-CD123 therapy, in patients with blastic plasmocytoid dendritic cell neoplasm: Sub-analysis of a pivotal trial by age and baseline disease involvement","volume":"22","author":"Pemmaraju","year":"2022","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.1182\/blood-2022-159970","article-title":"Tagraxofusp, an anti-CD123 therapy, in patients with blastic plasmocytoid dendritic cell neoplasm and prior or concomitant hematologic malignancies: Subgroup analysis of pivotal trial","volume":"140","author":"Pemmaraju","year":"2022","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13271","DOI":"10.1182\/blood-2022-158985","article-title":"Tagraxofusp administered concomitantly with intratechal chemotherapy in patients with BPDCN who either have or are considered high-risk to develop CNS disease is a safe and effective treatment strategy: An Italian multicenter experience","volume":"140","author":"Rivoli","year":"2022","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1182\/bloodadvances.2021006645","article-title":"Characteristics and outcomes of patients with blastic plasmocytoid dendritic cell neoplasm treated with frontline HCVAD","volume":"6","author":"Pemmaraju","year":"2022","journal-title":"Blood Adv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1182\/blood-2021-147486","article-title":"Safety and efficacy of combining tagraxofusp (SL-401) with azacytidine or azacytidine and venetoclax in a phase Ib study for CD123 positive AML, MDS or BPDCN","volume":"138","author":"Lane","year":"2021","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1158\/2159-8290.CD-16-0999","article-title":"Blastic plasmocytoid dendtitic cell neoplasm is dependent on BCL2 and sensitive to venetoclax","volume":"7","author":"Montero","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1056\/NEJMoa1815105","article-title":"More on blastic plasmocytoid dendritic cell neoplasms","volume":"380","author":"Pemmaraju","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_56","first-page":"E62","article-title":"Venetoclax and hypomethylating agents in older\/unfit patients with blastic plasmocytoid dendritic cell neoplasm","volume":"97","author":"Gongat","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/10428190701799035","article-title":"Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia","volume":"49","author":"Frankel","year":"2008","journal-title":"Leuk. Lymphoma"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11749","DOI":"10.1182\/blood-2022-170738","article-title":"Phase II study of tagraxofusp in newly diagnosed secondary acute myeloid leukemia (s-AML) after previous exposure to hypomethylating agents (TAGALONG study)","volume":"140","author":"Green","year":"2022","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1182\/blood-2022-164721","article-title":"Trial in progress: Tagraxofusp-based therapy to eradicate measurable residual disease of acute myelogenous leukemia prior to allogeneic hematopoietic cell transplantation","volume":"140","author":"Gaut","year":"2022","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1182\/blood.V130.Suppl_1.797.797","article-title":"Resistance to SL-401 in AML and BPDCN is associated with loss of diphtamide synthesis pathway enzyme DPH1 and is reversible by azacytidine","volume":"170","author":"Stephansky","year":"2017","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1172\/JCI128571","article-title":"DNA methyltransferase inhibition overcomes diphtamide pathway deficiencies underlying CD123-targeted treatment resistance","volume":"129","author":"Tagami","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e579","DOI":"10.1016\/j.clml.2021.02.008","article-title":"Combination of tagraxofusp and azacytidine is an effective option for relapsed blastic plasmocytoid dendritic cell neoplasm after allogeneic hematopoietic stem cell transplantation","volume":"21","author":"Wang","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12308-021-00479-z","article-title":"Relapse of tagraxofusp treated blastic plasmocytoid dendritic cell neoplasm with loss of CD123 expression","volume":"15","author":"Gulati","year":"2022","journal-title":"J. Hematopathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1182\/blood.V120.21.3598.3598","article-title":"CSL362: A monoclonal antibody to human interleukin 3 receptor (CD123), optimized for NK cell-mediated cytotoxicity of AML stem cells","volume":"120","author":"Busfield","year":"2012","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Testa, U., Pelosi, E., and Castelli, G. (2019). CD123 is a therapeutic target in the treatment of hematological malignancies. Cancers, 11.","DOI":"10.3390\/cancers11091358"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.3109\/10428194.2014.956316","article-title":"A phase I study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia","volume":"56","author":"He","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1182\/blood.V124.21.120.120","article-title":"First in man, phase I study of CSL362 (anti-IL3R\u03b1\/CD123) monoclonal antibody in patients with CD123+ acute myeloid leukemia in complete remission at high risk for early relapse","volume":"124","author":"Roboz","year":"2014","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/s41375-019-0645-z","article-title":"Single agent talacotuzumumab demonstrates limited efficacy but considerable toxicity in elderly high-risk MDS or AML patients failing hypomethylating agents","volume":"34","author":"Kubasch","year":"2020","journal-title":"Leukemia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41375-020-0773-5","article-title":"Safety and efficacy of talacotuzumumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: Results from a multicenter, randomized, phase 2\/3 study","volume":"35","author":"Montesinos","year":"2021","journal-title":"Leukemia"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1158\/1535-7163.MCT-16-0184","article-title":"A new class of antibody-drug conjugates with potent DNA alkylating activity","volume":"15","author":"Miller","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1158\/1535-7163.MCT-17-0940","article-title":"A DNA-interacting payload designed to eliminate cross-linking improves the therapeutic index of antibody-drug conjugates (ADCs)","volume":"17","author":"Miller","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1182\/bloodadvances.2018017517","article-title":"A CD123 targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells","volume":"2","author":"Kovtun","year":"2018","journal-title":"Blood Adv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1182\/blood-2019-128648","article-title":"Clinical profile of IMGN632, a novel CD123-targeting antibody-drug conjugate (ADC), in patients with relapsed\/refractory (R\/R) acute myeloid leukemia (AML) or blastic plasmacytoid dendritic cell neoplasm (BPDCN)","volume":"134","author":"Daver","year":"2019","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"PF201","DOI":"10.1097\/01.HS9.0000559020.72361.fa","article-title":"The combination of IMGN632, a CD123-targetingn ADC, with venetoclax enhances anti-leukemic activity In Vitro and prolongs survival in vivo in preclinical models of human AML","volume":"3","author":"Adams","year":"2019","journal-title":"HemaSphere"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1182\/blood-2021-146503","article-title":"Safety and efficacy from a phase 1b\/2 study of IMGN632 in combination with azacytidine and venetoclax for patients with CD123-positive acute myeloid leukemia","volume":"138","author":"Daver","year":"2021","journal-title":"Blood"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1182\/blood-2022-158030","article-title":"Broad activity for the pivekimab sunirine (IMGN632), azacytidine, and venetoclax triplet in high-risk patients with relapsed\/refractory acute myeloid leukemia (AML)","volume":"140","author":"Daver","year":"2022","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1182\/blood-2021-146681","article-title":"A study of IMGN632, a novel CD123-targeting antibody-drug conjugate, for patients with frontline and relapsed\/refractory blastic plasmocytoid dendritic cell neoplasm (BPDCN)","volume":"138","author":"Pemmaraju","year":"2021","journal-title":"Blood"},{"key":"ref_78","unstructured":"(2022, December 20). ImmunoGen Provided Update on CREDENZA Study of Pivekimab (IMGN632) in Frontline BPDN. New Release. ImmunoGen, 31 August 2022. Available online: https:\/\/bit.ly\/3TucEam."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1158\/1535-7163.MCT-17-0742","article-title":"Characterization of SGN-CD123A, a potent CD123-directed antibody-drug conjugate for acute myeloid leukemia","volume":"17","author":"Li","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1158\/1078-0432.CCR-20-2149","article-title":"Development of highly optimized antibody-drug conjugates against CD33 and CD123 for acute myeloid leukemia","volume":"27","author":"Han","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/protein\/gzs040","article-title":"Engineering of a CD123xCD3 bispecific scFv immunofusion for the treatment of leukemia and elimination of leukemia stem cells","volume":"25","author":"Kuo","year":"2012","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1182\/blood.V122.21.360.360","article-title":"Targeting CD123 in leukemic stem cells using dual affinity re-targeting molecules (DARTs)","volume":"122","author":"Hussaini","year":"2013","journal-title":"Blood"},{"key":"ref_83","first-page":"289ra82","article-title":"A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: Preclinical activity and safety in nonhuman primates","volume":"7","author":"Chicili","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1182\/blood-2014-05-575704","article-title":"Targeting CD123 in acute myeloid leukemia using a T-cell directed dual affinity retargeting platform","volume":"127","author":"Rettig","year":"2016","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1182\/blood-2018-99-117085","article-title":"Phase 1 cohort expansion of Flotetuzumab, a CD123 \u00d7 CD3 bispecific DART protein in patients with relapsed\/refractory acute myeloid leukemia (AML)","volume":"132","author":"Uy","year":"2018","journal-title":"Blood"},{"key":"ref_86","first-page":"3942","article-title":"Immune gene expression profiling in children and adults with acute myeloid leukemia identifies distinct phenotypic patterns","volume":"130","author":"Vadakekolathu","year":"2017","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e444","DOI":"10.1182\/blood-2018-99-111539","article-title":"Adaptive immune gene signatures correlate with response to Flotetuzumab, a CD123 \u00d7 CD3 bispecific DART molecule, in patients with relapsed\/refractory acute myeloid leukemia","volume":"132","author":"Rutella","year":"2018","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1182\/blood.2020007732","article-title":"Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia","volume":"137","author":"Uy","year":"2021","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"eaaz0463","DOI":"10.1126\/scitranslmed.aaz0463","article-title":"Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia","volume":"12","author":"Vadadekolathu","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1182\/bloodadvances.2020002512","article-title":"TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in AML","volume":"4","author":"Vadadekolathu","year":"2020","journal-title":"Blood Adv."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Barwe, S.P., Kisielewski, A., Bonvini, E., Muth, J., Davidson-Moncada, J., Kolb, E.A., and Gopalakrishnapillai, A. (2022). Efficacy of flotetuzumab in combination with cytarabine in patient-derived xenograft models of pediatric acute myeloid leukemia. J. Clin. Med., 11.","DOI":"10.3390\/jcm11051333"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1182\/blood-2022-158029","article-title":"Safety and activity of flotetuzumab in pediatric and young adult patients with relapsed\/refractory acute myeloid leukemia: Results from the COG PEPN 1812 phase 1 trial","volume":"140","author":"Lamble","year":"2022","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Rimando, J.C., Chendamarai, E., Rettig, M.P., Jayasunghe, R.G., Cristopher, M., Ritchey, J.K., Christ, S., Kim, M., Bonvini, E., and DiPersio, J.F. (2022). Flotetuzumab and other T-cell immunotherapies upregulate MHC class II expression on acute myeloid leukemia cells. Blood, in press.","DOI":"10.1182\/blood.2022017795"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1182\/blood-2021-153192","article-title":"Combinatorial anti-tumor activity in animal models of novel CD123 \u00d7 CD3 bispecific Dart molecule (MGD024) with cytarabine, venetoclax or azacitidine supports combination therapy in acute myeloid leukemia","volume":"138","author":"Anderson","year":"2021","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11753","DOI":"10.1182\/blood-2022-159524","article-title":"A phase 1, first-in-human, dose-escalation study of MGD-024, a CD123 \u00d7 CD3 bispecific Dart molecule, in patients with relapsed or refractory CD123-positive (+) hematologic malignancies","volume":"140","author":"Winer","year":"2022","journal-title":"Blood"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1182\/blood-2018-99-119786","article-title":"Complete responses in relapsed\/refractory acute myeloid leukemia (AML) patients on a weekly dosing schedule of XmAb14045, a CD123 \u00d7 CD3 T cell-engaging bispecific antibody: Initial results of a phase I study","volume":"132","author":"Ravandi","year":"2018","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1182\/blood-2020-134746","article-title":"Complete responses in relapsed\/refractory acute myeloid leukemia (AML) patients on a weekly dosing schedule of vibecotamab (XmAb14045), a CD123 \u00d7 CD3 T cell-engaging bispecific antibody; initial results of a phase 1 study","volume":"136","author":"Ravandi","year":"2020","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Comeau, M.R., Gottschalk, R., Daugherty, M., Sewerty, T., Sewell, T., Misher, L., Banninck, J., Johnson, S., Parr, L., and Kumar, J. (April, January 29). APV0436, a bispecific anti-CD123 \u00d7 CD3 ADAPTIRTM molecule for redirected T-cell cytotoxicity with limited cytokine release, is well tolerated in repeated dose toxicology studies in cynomolgus macaques. Proceedings of the American Association for Cancer research Annual Meeting 2019, Atlanta, GA, USA.","DOI":"10.1158\/1538-7445.AM2019-LB-199"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Comeau, M.R., Miller, R.E., Banninck, J., Johnson, S., Bader, R., Gottschalk, R., Daugherty, M., Sewell, T., Misher, L., and Mitchell, D. (2018, January 14\u201318). APV0436, a bispecific anti-CD123 \u00d7 CD3 ADAPTIRTM molecule for redirected T-cell cytotoxicity, induces potent T cell activation, proliferation and cytotoxicity with limited cytokine release. Proceedings of the American Association for Cancer Research Annual Meeting 2018, Chicago, IL, USA.","DOI":"10.1158\/1538-7445.AM2018-1786"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Uckun, F.M., Lin, T.L., Mims, A.S., Patel, P., Lee, C., Shadidzaeh, A., Shami, P.J., Cull, E., Cogle, C.R., and Watts, J. (2021). A clinical phase 1B study of the CD3xCD123 bispecific antibody APV0463 in patients with relapsed\/refractory acute myeloid leukemia or myelodysplastic syndrome. Cancers, 13.","DOI":"10.3390\/cancers13164113"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6204","DOI":"10.1182\/blood-2022-167468","article-title":"Updated results from a Phase 1 study of APVO436, a novel bispecific anti-CD123xanti-CD3 AdaptirTM molecule, in relapsed\/refractory acute myeloid leukemia and myelodysplastic syndrome","volume":"140","author":"Watts","year":"2022","journal-title":"Blood"},{"key":"ref_102","unstructured":"Boyiadzis, M., Desai, P., Daskalakis, N., Donnellan, W., Ferrante, L., Goldberg, J.D., Grumwald, M.R., Guttke, C., Li, X., and Perez-Simon, J.A. (2022). First-in-human study of JNJ-63709178, a CD123\/CD3 targeting antibody, in relapsed\/refractory acute myeloid leukemia. Clin. Transl. Med., in press."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1182\/blood-2022-165817","article-title":"CD123 directed IgM antibody-based T-cell engager, IGM-2537, demonstrates potent in vitro and in vivo activity with minimal cytokine release","volume":"140","author":"Liu","year":"2022","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7476","DOI":"10.1182\/blood-2022-166000","article-title":"An open-label, first-in-human, dose-escalation study of SAR443579 administered as single agent by intravenous infusion in patients with relapsed or refractory acute myeloid leukemia (R\/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplasia (HR-MDS)","volume":"140","author":"Stein","year":"2022","journal-title":"Blood"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"967754","DOI":"10.3389\/fonc.2022.967754","article-title":"Chimeric antigen receptor T-cell therapy for T-ALL and AML","volume":"12","author":"Wei","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nm.4478","article-title":"A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects","volume":"24","author":"Kagoya","year":"2018","journal-title":"Nat. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1182\/blood-2012-12-474056","article-title":"T cells expressing CD123-specific cytolytic effector functions and anti-tumor effects against human acute myeloid leukemia","volume":"122","author":"Mardiros","year":"2013","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"PR14","DOI":"10.1158\/2326-6074.TUMIMM18-PR14","article-title":"CD123 CAR displays clinical activity in relapsed\/refractory (r\/r) acute myeloid leukemia (AML) and blastic plasmocytoid dendritic cell neoplasm (BPDCN): Safety and efficacy results from a phase 1 study","volume":"8","author":"Budde","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e458","DOI":"10.1038\/bcj.2016.61","article-title":"Switching CAR T cells on and off: A novel modular platform for retargeting of T cells to AML blasts","volume":"6","author":"Cartellieri","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.omto.2020.04.009","article-title":"Rapidly switchable universal CAR-T cells for treatment of CD123-positive leukemia","volume":"17","author":"Loff","year":"2020","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1945804","DOI":"10.1080\/2162402X.2021.1945804","article-title":"Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML","volume":"10","author":"Mayer","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1182\/blood.2020009759","article-title":"Proof of concept for a rapidly switchable universal CAR-T platform with UniCAR-T-CD123 in relapsed\/refractory AML","volume":"137","author":"Wermke","year":"2021","journal-title":"Blood"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1182\/blood-2022-168877","article-title":"Phase I dose escalation study of the rapidly switchable UniCAR-T-CD123 in relapsed\/refractory AML","volume":"140","author":"Ehninger","year":"2022","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.ymthe.2019.04.010","article-title":"Chimeric antigen receptors incorporating D domains targeting CD123 direct potent mono- and bi-specific antitumor cativity of T cells","volume":"27","author":"Qin","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.3389\/fimmu.2020.01787","article-title":"Decitabine-mediated epigenetic reprogramming enhances anti-leukemia efficacy of CD123-targeted chimeric antigen receptor T-cells","volume":"11","author":"You","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1038\/s41467-022-29668-9","article-title":"Allogeneic TCR\u03b1\u03b2 deficient CAR T-cells targeting CD123 in acute myeloid leukemia","volume":"13","author":"Sugita","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1182\/blood-2022-169928","article-title":"A phase I trial of UCART123v1.2, an anti-CD123 allogeneic CAR-T cell product, in adult patients with relapsed or refractory (R\/R) acute myeloid leukemia (AML)","volume":"140","author":"Sallman","year":"2022","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1182\/blood-2022-170201","article-title":"Safety and anti-leukemic activity of CD123-CAR T cells in pediatric patients with AML: Preliminary results from a phase 1 trial","volume":"140","author":"Naik","year":"2022","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e005400","DOI":"10.1136\/jitc-2022-005400","article-title":"Generation and proiof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia","volume":"10","author":"Martinez","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s13045-022-01376-3","article-title":"Safe and effective off-the-shelf immunotherapy based on CAR.CD123-NK for the treatment of acute myeloid leukemia","volume":"15","author":"Caruso","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"10275","DOI":"10.1182\/blood-2022-163299","article-title":"Bispecific CD33\/CD123 targeted chimeric antigen receptor T cells for the treatment of acute myeloid leukemia","volume":"140","author":"Boucher","year":"2022","journal-title":"Blood"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"880108","DOI":"10.3389\/fimmu.2022.880108","article-title":"Transgenic expression of IL15 retains CD123-redirected T cells in a less differentiated state resulting in improved anti-AML activity in autologous AML PDX models","volume":"13","author":"Ostermann","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1158\/2159-8290.CD-19-0945","article-title":"Tuning the antigen density requirement for CAR-T cell activity","volume":"10","author":"Majzner","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.ccell.2017.09.004","article-title":"Integrating proteomics and transcriptomics for systematic combinatorial chimeric antigen receptor therapy of AML","volume":"32","author":"Perna","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1182\/blood.2020006921","article-title":"CLCEC12A and CD33 coexpression as a preferential target for pediatric AML combinatorial immunotherapy","volume":"137","author":"Willier","year":"2021","journal-title":"Blood"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"5890","DOI":"10.1158\/1078-0432.CCR-18-3927","article-title":"Bispecific antibodies enable synthetic agonistic receptor-transduced T cells for tumor immunotherapy","volume":"25","author":"Karches","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1038\/s41375-020-01109-w","article-title":"A modular and controllable T cell therapy platform for acute myeloid leukemia","volume":"35","author":"Benmebarek","year":"2021","journal-title":"Leukemia"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fonc.2020.00262","article-title":"A bump in the road: How the hostile AML microenvironment affects CART cell therapy","volume":"10","author":"Epperly","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e159579","DOI":"10.1172\/JCI159579","article-title":"Immune dysfunction signatures predict outcome and define checkpoint blockade-unresponsive microenvirnments in acute myeloid leukemia","volume":"132","author":"Rutella","year":"2022","journal-title":"J. Clin. Investig."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2718\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:20:26Z","timestamp":1760120426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,1]]},"references-count":129,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032718"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032718","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,1]]}}}