Integrated High-Throughput Screen to Identify Novel Treatment Leads for Pediatric Acute Myeloid Leukemia

Using a panel of human cell lines representing subtypes associated with high-risk of relapse we combined high-throughput screening (HTS), intracellular accumulation assays, and in vivo efficacy studies to identify novel therapeutic strategies for pediatric acute myeloid leukemia (AML). We identified multiple drug classes with broad activity across multiple subtypes, including: cytotoxics, epigenetic modifiers, and targeted agents; select compounds were further evaluated using primary patient samples ex vivo. FDA-approved drugs (e.g. gemcitabine, cabazitaxel) not currently used to treat AML were identified to have greater anti-leukemic activity relative to the standard of care, cytarabine, both in vitro and in vivo. Our comprehensive approach provides advances in pre-clinical development of novel treatment strategies with potential for rapid clinical translation for pediatric AML.