{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:05:57Z","timestamp":1768525557792,"version":"3.49.0"},"posted":{"date-parts":[[2025,9,29]]},"group-title":"Cancer Biology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Most pediatric acute myeloid leukemia (pAML) patients achieve complete remission after chemotherapy, yet relapse is common, with nearly 40% ultimately dying of the disease. Prognosis is currently assessed using cytogenetic biomarkers and measurable residual disease after the first chemotherapy cycle, with the highest risk patients referred for stem cell transplantation (SCT) at first remission. Because aggressive therapies such as SCT are highly toxic, yet cures after relapse are rare, accurate early risk prediction is essential for improving outcomes. To address this need, we analyzed paired diagnosis\u2013relapse samples from 33 pAML patients at single-cell resolution and identified chemoresistant cell populations whose abundance at diagnosis significantly improved risk prediction. Incorporating the detection of these cell populations into our risk model revealed a previously unrecognized patient subgroup with a 5-year event-free survival rate below 40%. Although this subgroup represents only 20% of pAML cases, it accounted for half of the deaths among patients who do not receive SCT at first remission. Moreover, molecular characterization of these chemoresistant cell populations uncovered potential therapeutic targets and candidate interventions relevant to most high-risk patients, paving the way for more effective targeted treatments for high-risk pAML patients.<\/jats:p>","DOI":"10.1101\/2025.09.25.678688","type":"posted-content","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T16:10:13Z","timestamp":1759162213000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Chemoresistant Cell Populations Improves Risk Stratification and Therapy Prediction in Pediatric AML"],"prefix":"10.64898","author":[{"given":"Mohammad Javad","family":"NajafPanah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra M","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Rochette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohani","family":"Sandhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lana","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua-Sheng","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Epps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonal","family":"Somvanshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Zorman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rodriguez","family":"Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-4871","authenticated-orcid":false,"given":"Marianna","family":"Rapsomaniki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Unger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-7867","authenticated-orcid":false,"given":"Burkhard","family":"Becher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna S.","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsz-Kwong","family":"Man","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele S","family":"Redell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1215-4977","authenticated-orcid":false,"given":"Pavel","family":"Sumazin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025102309100706000_2025.09.25.678688v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4439"},{"key":"2025102309100706000_2025.09.25.678688v2.2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.55.3628"},{"key":"2025102309100706000_2025.09.25.678688v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.10.008"},{"key":"2025102309100706000_2025.09.25.678688v2.4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-408336"},{"key":"2025102309100706000_2025.09.25.678688v2.5","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2010.30.6829"},{"key":"2025102309100706000_2025.09.25.678688v2.6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024026598"},{"key":"2025102309100706000_2025.09.25.678688v2.7","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.220962"},{"key":"2025102309100706000_2025.09.25.678688v2.8","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11030504"},{"key":"2025102309100706000_2025.09.25.678688v2.9","unstructured":"Umeda, M. et al. 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