{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337663/"]},"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=GSE337663"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Therapy-persistent leukemia is selectively vulnerable to SLC23A1 restoration via targeting KHSRP (AML patient samples)","description":"Acute myeloid leukemia (AML) remains highly prone to relapse driven by therapy-persistent residual cells. To discover specific vulnerabilities in this population, we performed genome-wide CRISPR interference screens in AML cells treated with multiple agents. KHSRP was the top hit, whose depletion sensitized AML cells to therapy and substantially prolonged survival in treated AML-bearing mice. Profiling in vivo residual disease after therapy identified downregulation of the vitamin C and uric acid transporter SLC23A1 as a resistance mechanism. KHSRP depletion restored SLC23A1 through a previously unrecognized function by preventing ZC3H4-mediated nuclear mRNA degradation. KHSRP depletion therefore enhanced the synergistic cytotoxicity of vitamin C and uric acid, particularly in therapy-persistent leukemia cells. Re-expression of TET2 overrode the chemosensitizing effect of KHSRP depletion in TET2-mutant leukemia, suggesting that KHSRP phenotypes were linked to vitamin C and uric acid-mediated TET activation. These findings nominate targeting KHSRP to enhance treatment efficacy and selectively eradicate residual AML.","dates":{"publication":"2026/07/10"},"accession":"GSE337663","cross_references":{"GSM":["GSM9859246","GSM9859247","GSM9859248","GSM9859241","GSM9859242","GSM9859243","GSM9859244","GSM9859245"],"GPL":["24676"],"GSE":["337663"],"taxon":["Homo sapiens"]}}