GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327228/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327228GEOGSEfalseRNA Terminal Uridylyl-Transferases Are Druggable Vulnerabilities in AML, but are Dispensable for Normal Hematopoiesis [RNA-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.2026/06/24GSE327228GSM9797739GSM9651769GSM9797741GSM9797740GSM9797744GSM9797743GSM9797742GSM9797727GSM9797726GSM9797725GSM9797729GSM9797728GSM9651764GSM9651763GSM9651768GSM9651767GSM9651766GSM9651765GSM9797730GSM9797734GSM9797733GSM9797732GSM9797731GSM9797738GSM9797737GSM9797736GSM97977352424721626327228Mus musculus