Preclinical model of UBTF-TD leukemia shows in vivo sensitivity to menin inhibitor SNDX-5613. (A) Schematic of in vivo SNDX-5613 treatment of UBTF-TD PDX. (B) Kaplan-Meier curves of UBTF-TD PDX model treated with vehicle or SNDX-5613 (n = 6 per group). Treatment period is shaded in green. (C) IVIS images of mice treated with vehicle or SNDX-5613 over time. Treatment period is shaded in green. Luminescence is row normalized to each time point. (D) Human CD45 chimerism (% of live) in the peripheral blood of mice from panel B. Treatment period is shaded in green (∗∗∗∗ indicates P value < .0001, 2-stage step-up Benjamini, Krieger, and Yekutieli test). (E) Spleen weight of mice harvested after 5 weeks of treatment with SNDX-5613 or vehicle (n = 3 per group) (2-tailed unpaired t test). (F) Spleen size of mice from panel E. (G) H&E and human NuMA1 IHC staining of spleens from panel F. (H) Flow cytometry analysis of bone marrow isolated from mice from panel D (P values are calculated with 2-tailed unpaired t test). MFI of CD11b-APC/Cy7 and CD117-PE/Cy7 (left panel) and representative flow plot (right panel) are shown (P values are calculated with 2-tailed unpaired t test). (I) Schematic of serial transplant experiment. Cells from each group in panel E were plated onto methylcellulose (#H4435, STEMCELL Technologies) (n = 3) or serially transplant into NSG-SGM3 mice (n = 3). (J) CFU capacity of cells from panel I (P value was calculated using an unpaired, 2-tailed t test). (K) Peripheral blood chimerism of mice from panel I. P values were calculated using 2-stage step-up Benjamini, Krieger, and Yekutieli test. CFU, colony-forming unit; IVIS, in vivo imaging system; H&E, hematoxylin and eosin; IHC, immunohistochemistry; MFI, mean fluorescent intensity; P.O, per os.