Proteasome Inhibition Targets the KMT2A Transcriptional Complex

We quantitatively evaluated H2Bub and H3K79me2 epigenetic marks genome wide in a KMT2A rearranged B lineage acute lymphoblastic leukemia cell line after treatment with bortezomib over a 6 hour time course by ChIP-Rx. We identified rapid and concordant depletion of these epigenetic marks within two hours. To look at gene expression changes, RNA sequencing was performed on KMT2A rearranged B lineage acute lymphoblastic leukemia patient samples in the presence and absence of bortezomib exposure. Overall design: Examination of 2 different histone modifications in the SEM cell line following in vitro exposure to bortezomib by ChIP with reference exogenous genome (ChIP-Rx) using Drosophila S2 cells to allow quantitation over the 6 hour time course. 5 patient samples were exposed to bortezomib or DMSO for 20 hours followed by RNA sequencing to look at changes to gene expression that correlate with these histone modifications.