GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327125/primary200OKOtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327125GEOGSEfalseRNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis [SLAM-Seq]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.2026/06/24GSE327125GSM9648670GSM9648660GSM9648671GSM9648672GSM9648661GSM9648659GSM9648673GSM9648662GSM9648663GSM9648674GSM9648675GSM9648664GSM9648676GSM9648665GSM9648655GSM9648666GSM9648677GSM9648678GSM9648667GSM9648656GSM9648668GSM9648657GSM9648669GSM964865821626327125Mus musculus