Fig. 7: ENL remains bound to MLL oncoprotein target genes during treatment with the menin inhibitors.

a Genome Browser tracks showing MLL, menin, DOT1L and ENL bound to the MBNL1 locus in the B-ALL sample (top). In the patient-matched AML sample treated with the menin inhibitor only ENL remains bound (bottom). b Oncogene expression is significantly reduced in the AML after lineage switching. Bar height is the average of three qPCR biological replicates; Error bars = standard deviation, and the p value was computed using a two-tailed independent samples t-test; n = 3 qPCR biological replicates. c Reverse transcriptase PCR with two primer sets confirms the MLL::ENL oncogene is expressed in the AML treated with the menin inhibitor (expected size for 1 = 159 bp, and 2 = 150 bp). d Scatterplot comparing the normalized menin levels in the B-ALL and the AML sample treated with the menin inhibitor over an internal control group of oncoprotein-target sites (gray) the B-ALL-specific program (gold) and the GMP-like program (pink). e Same as (d) but showing the ENL signal persists over many of the oncoprotein-target genes in the AML sample. f Boxplot comparing ENL signal over an internal control group of oncoprotein-target genes (gray, n = 1595) the B-ALL-specific program (gold, n = 52) and the GMP-like program (pink, n = 45). p values were computed using a two-sided Mann-Whitney U Test with a Bonferroni correction for multiple hypothesis testing; boxplot center lines = median, box limits = first and third quartiles, whiskers = 1.5 times the interquartile range (IQR). g The menin inhibitor disrupts MLL oncoproteins, but ENL accumulation persists on oncoprotein targets in the GMP-like program. Source data are provided as a Source Data file.