Extended Data Fig. 1: Revumenib suppresses both KMT2Ar and NPM1-mutant AML in preclinical models of leukaemia.

NSG mice were engrafted with the KMT2Ar cell line MOLM-13 (a; n = 10) or patient derived xenografts (PDX) harbouring either a KMT2Ar (d; n = 5) or NPM1 mutation (g; n = 5). Mice were treated for 28 days with revumenib, which was formulated in chow, across a dose range of 0.025% to 0.2% (a) or at 0.1% fixed dose (d, g). Leukaemic burden (CD45+) was assessed at end of treatment (b; 0.025%: n = 3; 0.05-0.2%: n = 5, data represent mean ± SEM) or throughout the study (d, g; data represent mean ± SEM). For MOLM-13 engrafted mice, revumenib showed clear dose-dependent exposure (c; n = 3 with 3 individual measurements per timepoint and dose, data represent mean ± SD), which translated into dose-responsive effect on survival benefit (a) and leukaemic burden at end of treatment (b). Similarly, revumenib treatment of the PDX models led to significant suppression of leukaemic burden and significant survival benefit in each (d, g). P-values were determined by log-rank (Mantel–Cox) tests. Adjustments were not made for multiple comparisons. Revumenib treatment also led to broad changes in the transcriptional program (f, i; n = 3 per treatment group; GEO accession number for RNAseq data, GSE216730) with GSEA results consistent with previously reported signatures (e, h; n = 3 per treatment group). GSEA, gene set enrichment analysis; NES, normalized enrichment score; NSG, NOD scid gamma; PDX, patient-derived xenograft; SD, standard deviation; SEM, standard error of the mean.