biostudies-literatureH Elsayed AU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)American Cancer SocietyAmerican Cancer Society (American Cancer Society, Inc.)U.S. Department of Health &amp; Human Services | NIH | National Cancer InstituteNHGRI NIH HHSNCI NIH HHS168https://www.ebi.ac.uk/biostudies/studies/S-EPMC11294346biostudies-literatureUnknown8(1)In this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084 ) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.0001). ADE-RS5 was integrated with a previously defined leukemic-stemness signature (pLSC6) to classify patients into four groups. ADE-RS5, pLSC6 and integrated-score was evaluated for association with outcome in one of the largest assembly of ~3600 AML patients from 10 independent cohorts (1861 pediatric and 1773 adult AML). Patients with high ADE-RS5 had poor outcome in validation cohorts and the pNPJ precision oncologyIntegrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials.PMC11294346U10 CA098543P30 CA247796U10 CA180886T32 HG008958SAP 21-061-01R01 CA132946R01CA132946U10 CA180899U10 CA098413Rubnitz JRibeiro RCHebert JRichard-Carpentier GZwaan CMMeshinchi SNguyen NHKLamba JKMarrero RJWu HGamis APounds SH Elsayed ANi YValk PJCao XTobias HAplenc RBeliveau FAlonzo TAKolb EAfalseIntegrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials.In this study, we leveraged machine-learning tools by evaluating expression of genes of pharmacological relevance to standard-AML chemotherapy (ara-C/daunorubicin/etoposide) in a discovery-cohort of pediatric AML patients (N = 163; NCT00136084 ) and defined a 5-gene-drug resistance score (ADE-RS5) that was predictive of outcome (high MRD1 positivity p = 0.013; lower EFS p < 0.0001 and OS p < 0.0001). ADE-RS5 was integrated with a previously defined leukemic-stemness signature (pLSC6) to classify patients into four groups. ADE-RS5, pLSC6 and integrated-score was evaluated for association with outcome in one of the largest assembly of ~3600 AML patients from 10 independent cohorts (1861 pediatric and 1773 adult AML). Patients with high ADE-RS5 had poor outcome in validation cohorts and the p2024-01-01T00:00:00Z2024 Aug2026-07-15T08:06:09.169Z2024-11-08T23:09:33.678ZS-EPMC112943463909019210.1038/s41698-024-00643-5