biostudies-literatureNguyen NHKNHGRI NIH HHSNCI NIH HHS1769-1783https://www.ebi.ac.uk/biostudies/studies/S-EPMC10182178biostudies-literatureUnknown7(9)Etoposide is used to treat a wide range of malignant cancers, including acute myeloid leukemia (AML) in children. Despite the use of intensive chemotherapeutic regimens containing etoposide, a significant proportion of pediatric patients with AML become resistant to treatment and relapse, leading to poor survival. This poses a pressing clinical challenge to identify mechanisms underlying drug resistance to enable effective pharmacologic targeting. We performed a genome-wide CRISPR/Cas9 synthetic-lethal screening to identify functional modulators of etoposide response in leukemic cell line and integrated results from CRISPR-screen with gene expression and clinical outcomes in pediatric patients with AML treated with etoposide-containing regimen. Our results confirmed the involvement of wellBlood advancesGenome-wide CRISPR/Cas9 screen identifies etoposide response modulators associated with clinical outcomes in pediatric AML.PMC10182178T32 HG008958R01 CA132946Seligson NElsayed AHRubnitz JPounds SBLoguinov ARafiee RNguyen NHKde Jesus Sosa AKLamba JKSobh ADowning JCao XTagmount AGbadamosi MVulpe CDCogle CRRibeiro RfalseGenome-wide CRISPR/Cas9 screen identifies etoposide response modulators associated with clinical outcomes in pediatric AML.Etoposide is used to treat a wide range of malignant cancers, including acute myeloid leukemia (AML) in children. Despite the use of intensive chemotherapeutic regimens containing etoposide, a significant proportion of pediatric patients with AML become resistant to treatment and relapse, leading to poor survival. This poses a pressing clinical challenge to identify mechanisms underlying drug resistance to enable effective pharmacologic targeting. We performed a genome-wide CRISPR/Cas9 synthetic-lethal screening to identify functional modulators of etoposide response in leukemic cell line and integrated results from CRISPR-screen with gene expression and clinical outcomes in pediatric patients with AML treated with etoposide-containing regimen. Our results confirmed the involvement of well2023-01-01T00:00:00Z2023 May2026-07-15T01:42:15.682Z2025-04-05T21:07:44.637ZS-EPMC101821783611189110.1182/bloodadvances.2022007934