GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311841/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311841GEOGSEfalseRNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal HematopoiesisAcute 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.2026/07/17GSE311841GSM9333301GSM9333300GSM9333295GSM9333294GSM9333297GSM9333296GSM9333299GSM933329824247311841Mus musculus