UBTF-TD leukemias are sensitive to menin inhibitors. (A) Schema for in vitro culture of primary UBTF-TD AMLs. (B) Primary tumors from 5 individual patients (Pt1-5) harboring a UBTF-TD alteration treated with menin inhibitor SNDX-5613 in vitro. Primary sample from a single patient with a RUNX1::RUNX1T1 alteration was used as a control. (C) MEIS1 mRNA steady-state levels in patient cells treated with SNDX-5613. (D) CFU capacity of UBTF-TD leukemias after exposure to SNDX-5613. Cells from Pt4 and Pt5 were treated with SNDX-5613 (250nM, SFEMII media) for 12 days and then plated in methylcellulose (#H4435, STEMCELL Technologies). (E) Heatmap depicting mRNA levels of the top 30 differentially expressed genes after 7 days of treatment with SNDX-5613. The divergent color map depicts row normalized expression. (F) CFU of UBTF-TD PDX cells plated in methylcellulose (H4435, STEMCELL) and treated with DMSO or SNDX-5613 (100nM, 500nM, 1μM). (G) Immunophenotyping of cells from panel F for stem-cell marker CD117 and CD11b. (H) Annexin V+ staining of cells from panel F. For panels F and G, statistical significances were calculated using a 1-way analysis of variance test with Dunnett’s multiple comparison adjustment using DMSO as control. CFU, colony forming unit; DMSO, dimethyl sulfoxide.