{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338690/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338690"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacological inhibition of PRKDC-mediated DNA damage response by 3-hydroxyflavone selectively alleviates MLL-rearranged acute myeloid leukemia","description":"Genetic rearrangements involving mixed lineage leukemia (MLL-r) in acute myeloid leukemia (AML) have been associated with resistance to chemotherapy, and there is currently a clinical unmet need for effective targeted therapies. In this study, we performed high-throughput drug screening and identified 3-Hydroxyflavone (3-HF) as a selective inhibitor of the survival and growth of MLL-r AML cells, while having minimal effects on leukemia cells with wildtype MLL. Mechanistically, 3-HF suppresses the transcription of MLL-targeted genes and exerts antileukemic activity by disrupting PRKDC-mediated DNA damage repair. Additionally, 3-HF enhances chemosensitivity in MLL-r AML cells and demonstrates synergistic antileukemic effects when combined with cytarabine, a standard chemotherapy agent, both in vitro and in vivo using two distinct mouse models of murine MLL-AF9 and human MLL-AF4 leukemia. Our findings provide a novel strategy and targeted therapeutic drug disrupting PRKDC-mediated DNA damage repair pathways for MLL-r leukemia.","dates":{"publication":"2026/07/21"},"accession":"GSE338690","cross_references":{"GSM":["GSM9879678","GSM9879667","GSM9879677","GSM9879666","GSM9879669","GSM9879679","GSM9879668","GSM9879663","GSM9879674","GSM9879673","GSM9879662","GSM9879665","GSM9879676","GSM9879675","GSM9879664","GSM9879670","GSM9879672","GSM9879671"],"GPL":["16791"],"GSE":["338690"],"taxon":["Homo sapiens"]}}