Fig. 6: The Menin/KMT2A interaction is a therapeutic target in human MN1- driven AML.

A Cell growth of UCSD-AML1 cells [MN1-ETV6] and Kasumi-1 cells [RUNX1-RUNXT1] plated with DMSO or VTP50469 at the indicated doses shown as absolute cell numbers over 16 days of treatment. Error bars represent mean ± SEM of two biological replicates. B Dose response (IC50) of UCSD-AML1 and control cell lines (KMT2A-r: MV4;11, Molm14, THP1, NPM1c: OCI-AML3, negative control RUNX1-RUNXT1: Kasumi, BCR-ABL: K562). Error bars represent mean ± SEM of three technical replicates. C Schematic representing the UCSD-AML1 xenograft experimental set up. NSGS mice were transplanted at D0. VTP50469 chow was started at D14 post-transplant for a total of 25 days. Leukemia burden was assessed at Time Point 1 (TP1), after 14 days on chow, at D28 post-transplant and at Time Point 2 (TP2), 7 days after discontinuing chow, at D47 post-transplant. D Leukemia burden in the bone marrow at TP1 (left panel), as well as bone marrow (middle panel) and the spleen (right panel) at TP2, in VTP50469 versus control treated mice assessed by the percentage of human CD45⁺, murine CD45⁻ cells. Error bars represent mean ± SEM of biological replicates (n = 5 animals per condition, unpaired double-sided t-test.). E Survival of mice NSG mice transplanted with UCSD-AML1 cells and treated with VTP50469 or control chow. VTP50469 chow was started at D14 post-transplant and continued throughout the experiment. Kaplan–Meier estimate, p < 0.0001 n = 10 animals per condition. F Leukemia burden in the bone marrow (left) and the spleen (right) at necropsy in VTP50469 versus control treated mice assessed by the percentage of human CD45⁺, murine CD45⁻ cells. Error bars represent mean ± SEM, n = 10 animals per condition, unpaired double-sided t-test.