Fig. 1: Genomic enrichment of MLL oncoproteins is highly heterogeneous.

a We performed AutoCUT&RUN on a collection of MLLr cell lines and patient samples including a range of patient ages and lineage subtypes. b Comparison of CUT&RUN profiles using antibodies targeting the MLL N-terminal (red) and C-terminal (blue) regions can discriminate the oncoprotein-binding sites from wild-type MLL binding sites. c When the same magnitude and significance thresholds are applied to the MLL N versus C terminal profiles, we identify many more oncoprotein-target sites (red dots) in the SEM MLLr cell line than the CD34+ wild type control sample. p values were computed from the mean and standard deviation of Monte Carlo sampling of the N/C scores (n = 1000 samples) of each genomic interval; p values were corrected for multiple hypothesis testing using the Benjamini/Hochberg method. d Principal component analysis and UMAP embedding splits the MLLr samples into four clusters that are outlined with dotted lines; samples are colored according to the lineage subtype; patient-matched lineage-switching samples are indicated by the Greek letters α, β, γ. e The UMAP embedding from (d) but colored according to the MLL-oncoprotein-fusion partner. f Same as (d) colored according to the average oncoprotein scores (N/C terminal magnitude x significance). g The UMAP clusters capture differences in the global oncoprotein levels. p values were computed using a two-tailed independent samples t-test; Cluster 1 n = 13 samples, Cluster 2 n = 6 samples, Cluster 3 n = 15 samples, Cluster 4 n = 5 samples; boxplot center lines = median, box limits = first and third quartiles, whiskers = 1.5 times the interquartile range (IQR). h The average oncoprotein scores scale with the relative oncogene expression. Samples are grouped and colored according to the minimal MLL-fusion-partner exon junctions. Two MLL::AFDN samples were identified as outliers: ML-2 is indicated by a star and A70498 by an asterisk. Dotted lines indicate the regression, error bars indicate the standard deviation of the mean of three qPCR biological replicates. Source data are provided as a Source Data file.