{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T23:48:00Z","timestamp":1794440880628,"version":"4.9.1"},"reference-count":47,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 \u00d7 CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) AML (n = 22) and 45 BM samples from patients who received flotetuzumab for relapsed\/refractory (R\/R) AML (15 cases with TP53 mutations and\/or 17p deletion). The comparison between TP53-mutated and TP53-WT primary BM samples showed higher expression of IFNG, FOXP3, immune checkpoints, markers of immune senescence, and phosphatidylinositol 3-kinase-Akt and NF-\u03baB signaling intermediates in the former cohort and allowed the discovery of a 34-gene immune classifier prognostic for survival in independent validation series. Finally, 7 out of 15 patients (47%) with R\/R AML and TP53 abnormalities showed complete responses to flotetuzumab (&amp;lt;5% BM blasts) on the CP-MGD006-01 clinical trial (NCT #02152956) and had significantly higher tumor inflammation signature, FOXP3, CD8, inflammatory chemokine, and PD1 gene expression scores at baseline compared with nonresponders. Patients with TP53 abnormalities who achieved a complete response experienced prolonged survival (median, 10.3 months; range, 3.3-21.3 months). These results encourage further study of flotetuzumab immunotherapy in patients with TP53-mutated AML.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002512","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T15:37:19Z","timestamp":1602776239000},"page":"5011-5024","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":151,"title":["TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in AML"],"prefix":"10.1182","volume":"4","author":[{"given":"Jayakumar","family":"Vadakekolathu","sequence":"first","affiliation":[{"name":"John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Lai","sequence":"additional","affiliation":[{"name":"MedStar Georgetown University Hospital\u2019s Lombardi Comprehensive Cancer Center, Washington, DC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Reeder","sequence":"additional","affiliation":[{"name":"John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Church","sequence":"additional","affiliation":[{"name":"NanoString Technologies, Inc., Seattle, WA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tressa","family":"Hood","sequence":"additional","affiliation":[{"name":"NanoString Technologies, Inc., Seattle, WA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-6301","authenticated-orcid":false,"given":"Anbarasu","family":"Lourdusamy","sequence":"additional","affiliation":[{"name":"School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Rettig","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Aldoss","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-5902","authenticated-orcid":false,"given":"Anjali S.","family":"Advani","sequence":"additional","affiliation":[{"name":"Leukemia Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Godwin","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute, Providence Cancer Centre, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Wieduwilt","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, La Jolla, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Arellano","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University, Atlanta, GA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Muth","sequence":"additional","affiliation":[{"name":"MacroGenics, Inc., Rockville, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-0370","authenticated-orcid":false,"given":"Tung On","family":"Yau","sequence":"additional","affiliation":[{"name":"John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Ravandi","sequence":"additional","affiliation":[{"name":"Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra","family":"Sweet","sequence":"additional","affiliation":[{"name":"Moffitt Cancer Center, Tampa, FL;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Altmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma A.","family":"Foulds","sequence":"additional","affiliation":[{"name":"John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"St\u00f6lzel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Moritz","family":"Middeke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Ciciarello","sequence":"additional","affiliation":[{"name":"Institute of Hematology \u201cL. and A. Ser\u00e1gnoli,\" Department of Hematology and Oncology, University Hospital S. Orsola-Malpighi, Bologna, Italy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Curti","sequence":"additional","affiliation":[{"name":"Institute of Hematology \u201cL. and A. Ser\u00e1gnoli,\" Department of Hematology and Oncology, University Hospital S. Orsola-Malpighi, Bologna, Italy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J. M.","family":"Valk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus Medical Centre, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8982-5217","authenticated-orcid":false,"given":"Bob","family":"L\u00f6wenberg","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus Medical Centre, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Gojo","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bornh\u00e4user","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, 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