{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326857/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Non-coding RNA profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326857"],"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 hematopoietic stem and progenitor cells (HSPCs). Current treatments often fail to eradicate AML; therefore, new therapeutic strategies are essential. Here, we reveal that RNA Terminal-Uridylyl-Transferase-Enzymes 4 and 7 (TUT4/7) are druggable therapeutic targets, whose genetic deletion suppresses AML growth, induces apoptosis and improves the survival in leukemic mouse models. Notably, a pre-clinical TUT4/7 inhibitor promotes cell death in AML patient samples and synergizes with venetoclax. Mechanistically, TUT4/7 inactivation suppresses mevalonate pathway gene expression, compromising the cholesterol synthesis pathway. Current AML therapies often cause severe hematopoietic toxicity. Although Tut4/7 deletion results in inflammatory activation throughout the hematopoietic system, this is permissive to a normal lifespan and Tut4/7-deficiency does not compromise HSPC function. Together, these findings identify TUT4/7 as druggable targets, whose inactivation suppresses AML while sparing normal hematopoiesis. In combination with venetoclax this represents a promising therapeutic strategy.","dates":{"publication":"2026/06/24"},"accession":"GSE326857","cross_references":{"GSM":["GSM9641373","GSM9641365","GSM9641364","GSM9641372","GSM9641371","GSM9641367","GSM9641366","GSM9641369","GSM9641368"],"GPL":["23969"],"GSE":["326857"],"taxon":["Mus musculus"]}}