{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327228/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"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=GSE327228"],"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 [RNA-seq]","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":"GSE327228","cross_references":{"GSM":["GSM9797739","GSM9651769","GSM9797741","GSM9797740","GSM9797744","GSM9797743","GSM9797742","GSM9797727","GSM9797726","GSM9797725","GSM9797729","GSM9797728","GSM9651764","GSM9651763","GSM9651768","GSM9651767","GSM9651766","GSM9651765","GSM9797730","GSM9797734","GSM9797733","GSM9797732","GSM9797731","GSM9797738","GSM9797737","GSM9797736","GSM9797735"],"GPL":["24247","21626"],"GSE":["327228"],"taxon":["Mus musculus"]}}