Menin inhibition in UBTF-ITD AML. (A) UBTF is recruited to ribosomal DNA (rDNA) loci in normal cells. (B) In AML with UBTF-ITD, the mutated UBTF is recruited to both rDNA loci and sites of KMT2A/menin binding, including the HOXA and HOXB cluster, resulting in aberrant expression of these genes. (C) Degradation of UBFT-ITD results in transcriptional downregulation of HOXA and HOXB cluster genes, despite maintained KMT2A and menin binding. (D) Inhibition of the menin:KMT2A interaction also results in downregulation of HOXA and HOXB cluster genes and induces differentiation in UBTF-ITD leukemia cells. Created with BioRender.com.