{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:30:29Z","timestamp":1777865429174,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014547","name":"Parker Institute for Cancer Immunotherapy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014547","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006063","name":"Paul and Daisy Soros Fellowships for New Americans","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006063","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"}]},{"DOI":"10.13039\/100006352","name":"Virginia and D.K. Ludwig Fund for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric acute myeloid leukemia (pAML) is comprised of a diverse set of oncogenic drivers (ODs) that have been risk\u2010stratified to inform prognosis and therapeutic decision\u2010making. Despite proteomic, transcriptomic, genetic, and epigenetic characterization of the pAML landscape, questions still remain about why certain ODs have poorer prognoses than others.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyze a large pAML bulk\u2010RNA dataset (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009435) and organize ODs along an axis of transcriptomic diversity by calculating the Simpson Diversity Index (SDI) of individual ODs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      When comparing patients with low diversity ODs to patients with high diversity ODs, we observe poorer overall survival (HR\u2009=\u20091.877, 95% CI: 1.377\u20132.558,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002) among patients harboring high diversity ODs in addition to an enrichment of stemness\u2010related genes. We observe poorer survival of patients with high diversity ODs even when comparing patients with similar transcriptomic profiles (HR\u2009=\u20093.443, 95% CI: 1.817\u20136.525,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0028).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identify a link between transcriptomic diversity, expression of stemness\u2010related genes, and clinical outcome. Higher transcriptomic heterogeneity exhibited by high diversity ODs warrants further attention when identifying patients who can benefit from novel or high\u2010intensity therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71325","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:50:13Z","timestamp":1762159813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Diversity of Pediatric Acute Myeloid Leukemia Genetic Drivers Correlates With Clinical Outcome and Expression of Stemness\u2010Related Genes"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-0731","authenticated-orcid":false,"given":"Quenton Rashawn","family":"Bubb","sequence":"first","affiliation":[{"name":"Stem Cell Biology and Regenerative Medicine Graduate Program, Medical Scientist Training Program Stanford University School of Medicine  Stanford California USA"},{"name":"Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine  Stanford California USA"},{"name":"Institute for Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Sotillo","sequence":"additional","affiliation":[{"name":"Stanford Cancer Institute, Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca M.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystal L.","family":"Mackall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine  Stanford California USA"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine  Stanford California USA"},{"name":"Division of Blood and Stem Cell Transplantation and Cell Therapy, Department of Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja A.","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Czechowicz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine  Stanford California USA"},{"name":"Institute for Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4439"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-21-0049"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33244-6"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01640-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20598"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0604-8"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30584"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3772"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10725"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3909"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0436-0"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/163688a0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu393"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.32614\/RJ-2021-053"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.1.224-234.2001"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01213-w"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9241"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.161257"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.361"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011771"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0424"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-024-01004-y"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14112764"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05812-3"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omton.2025.200944"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71325","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.71325","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.71325","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:31:55Z","timestamp":1777530715000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.71325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":25,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/cam4.71325"],"URL":"https:\/\/doi.org\/10.1002\/cam4.71325","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71325"}}