Fig. 7

Menin mutated cells with acquired resistance to Menin-inhibition retain sensitivity to immunoproteasome inhibition and preserved activity of combinatorial treatment strategies against MEN1-mutated clones may blunt outgrowth of resistant cells. A Relative growth to DMSO of wild-type MV-4;11 (MV-4;11 WT) and two MV-4;11 cell lines containing mutations in MEN1 (MV-4;11 M327I, methionine to isoleucine change at position 327; MV-4;11 T349M, threonine to methionine at position 349) after treatment with PR-957 (50 nM, 100 nM). n = 4 independent experiments; mean with SD. B Schematic representation of the competitive transplantation of 5 × 10⁴ MV-4;11 M327I-RFP⁺ cells and 1 × 10⁵ MV-4;11 WT-BFP⁺ cells (transplanted one week later) into NXG mice. Recipient mice were treated for 3 weeks with food supplemented with 0.05% Revumenib, Revumenib + PR-957 (6 mg/kg, 5 days/week, at week 1 and week 3) or control diet. C Immunophenotyping of human CD45 + (hCD45 +) cells in the BM of NXG mice after in vivo treatment with Revumenib, Revumenib + PR-957 or control diet. n = 10 mice per treatment. D Representative flow cytometry plots (3 per cohort) showing the percentage of hCD45 + and percentage of RFP + hCD45 + and BFP + hCD45 + bone marrow cells in the control, Revumenib-treated and Revumenib + PR-957 treated mice. E Pie charts depicting the number of mice expressing MV-4;11 WT-BFP + cells (blue), MV-4;11 M327I-RFP + cells (red) or no RFP + / BFP + cells (negative, grey), respectively