{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:53:07Z","timestamp":1782449587607,"version":"3.54.5"},"reference-count":27,"publisher":"American Society of Hematology","issue":"26","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,25]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Acute myeloid leukemia (AML) is a multiclonal disease, existing as a milieu of clones with unique but related genotypes as initiating clones acquire subsequent mutations. However, bulk sequencing cannot fully capture AML clonal architecture or the clonal evolution that occurs as patients undergo therapy. To interrogate clonal evolution, we performed simultaneous single-cell molecular profiling and immunophenotyping on 43 samples from 32 patients with NPM1 (nucleophosmin 1)\u2013mutated AML at different time points in disease progression. Here, we show that diagnosis and relapse AML samples display similar clonal architecture patterns, but signaling mutations drive increased clonal complexity, specifically at relapse, which correlates with overall survival. We uncovered unique genotype-immunophenotype relationships regardless of disease state, suggesting leukemic lineage trajectories can be hard-wired by the mutations present. Analysis of longitudinal samples from patients on front-line AML therapy identified dynamic clonal and immunophenotypic changes consistent with the genotype-immunophenotype relationships we identified.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030772","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T16:23:42Z","timestamp":1775665422000},"page":"3209-3216","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":3,"title":["Genotype-immunophenotype relationships in\n                    <i>NPM1<\/i>\n                    -mutated AML clonal evolution uncovered by single-cell multiomic analysis"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1259-3988","authenticated-orcid":false,"given":"Morgan","family":"Drucker","sequence":"first","affiliation":[{"name":"1Division of Oncology, Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"2Department of Pediatrics, University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Lee","sequence":"additional","affiliation":[{"name":"3University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bowman","sequence":"additional","affiliation":[{"name":"4Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7966-8748","authenticated-orcid":false,"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"5Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8407-9937","authenticated-orcid":false,"given":"Bailee N.","family":"Kain","sequence":"additional","affiliation":[{"name":"5Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7796-0251","authenticated-orcid":false,"given":"Deedra","family":"Nicolet","sequence":"additional","affiliation":[{"name":"6The Ohio State University Comprehensive Cancer Center, Columbus, OH"},{"name":"7Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9982-9654","authenticated-orcid":false,"given":"Roopsha","family":"Bandopadhyay","sequence":"additional","affiliation":[{"name":"4Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-7102","authenticated-orcid":false,"given":"Varsha","family":"Singh","sequence":"additional","affiliation":[{"name":"4Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-4125","authenticated-orcid":false,"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"5Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-2633","authenticated-orcid":false,"given":"Richard M.","family":"Stone","sequence":"additional","affiliation":[{"name":"8Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7617-8356","authenticated-orcid":false,"given":"Caner","family":"Saygin","sequence":"additional","affiliation":[{"name":"9Department of Medicine, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1408-5063","authenticated-orcid":false,"given":"Krzysztof","family":"Mr\u00f3zek","sequence":"additional","affiliation":[{"name":"6The Ohio State University Comprehensive Cancer Center, Columbus, OH"},{"name":"7Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9844-730X","authenticated-orcid":false,"given":"Andrew J.","family":"Carroll","sequence":"additional","affiliation":[{"name":"10Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5771-7462","authenticated-orcid":false,"given":"Daniel T.","family":"Starczynowski","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, University of Cincinnati, Cincinnati, OH"},{"name":"11Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"12University of Cincinnati Cancer Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7884-1905","authenticated-orcid":false,"given":"Ross L.","family":"Levine","sequence":"additional","affiliation":[{"name":"13Human Oncology and Pathogenesis Program, Molecular Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"14Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"15Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-1000","authenticated-orcid":false,"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"16Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-2469","authenticated-orcid":false,"given":"Nathan","family":"Salomonis","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, University of Cincinnati, Cincinnati, OH"},{"name":"17Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7711-0732","authenticated-orcid":false,"given":"Sarah J.","family":"Skuli","sequence":"additional","affiliation":[{"name":"12University of Cincinnati Cancer Center, Cincinnati, OH"},{"name":"18Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8162-6758","authenticated-orcid":false,"given":"H. Leighton","family":"Grimes","sequence":"additional","affiliation":[{"name":"2Department of Pediatrics, University of Cincinnati, Cincinnati, OH"},{"name":"5Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"},{"name":"11Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6442-1419","authenticated-orcid":false,"given":"Ann-Kathrin","family":"Eisfeld","sequence":"additional","affiliation":[{"name":"6The Ohio State University Comprehensive Cancer Center, Columbus, OH"},{"name":"7Clara D. 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