{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311841/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311841"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis","description":"Acute myeloid leukemia (AML) is an aggressive hematological malignancy arising from blood-forming hematopoietic stem and progenitor cells (HSPCs). Current therapies often fail to eradicate AML, therefore, identification of novel therapeutic targets is essential. Here, we reveal Terminal Uridylyl Transferase Enzymes 4 and 7 (TUT4/7) as druggable novel therapeutic targets whose genetic deletion in AML suppresses growth, induces apoptosis and improves the survival of in vivo mouse models. Use of a pre-clinical TUT4/7 inhibitor is cytotoxic to AML patient samples, dysregulates mevalonate pathway genes and synergizes with Venetoclax. AML therapies are often limited by hematopoietic toxicity. Remarkably, we find that although Tut4/7 deletion results in mild inflammatory activation throughout the hematopoietic system, this activation is largely permissive, and mice exhibit no overt pathology for at least one year. Thus, we reveal TUT4/7 as novel druggable therapeutic targets, whose inactivation compromises AML while sparing normal hematopoiesis.","dates":{"publication":"2026/07/17"},"accession":"GSE311841","cross_references":{"GSM":["GSM9333301","GSM9333300","GSM9333295","GSM9333294","GSM9333297","GSM9333296","GSM9333299","GSM9333298"],"GPL":["24247"],"GSE":["311841"],"taxon":["Mus musculus"]}}