Abstract Acute myeloid and lymphoid leukemias often harbor chromosomal translocations involving the Mixed Lineage Leukemia-1 gene, encoding the KMT2A lysine methyltransferase. The most common translocations produce in-frame fusions of KMT2A to other chromatin regulatory proteins. Here we develop a strategy to map the genome-wide occupancy of oncogenic KMT2A fusion proteins in primary patient samples regardless of fusion partner. By modifying the versatile CUT&amp;Tag method for full automation we identify common and tumor-specific patterns of aberrant chromatin regulation induced by different KMT2A fusion proteins. Integration of automated and single-cell CUT&amp;Tag uncovers epigenomic heterogeneity within patient samples and predicts sensitivity to therapeutic agents.

Automated CUT&amp;Tag profiling of chromatin heterogeneity in mixed-lineage leukemia

Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia