RNA-seq analysis of human KMT2A rearranged Molm14 AML cell line treated with DOT1L and/or EZH2 inhibitor

The histone methyltransferases DOT1L (H3K79me1,2,3 KMT, "activating" chromatin mark) and EZH2 (H3K27me1,2,3 KMT, "silencing" mark) have both been shown to be required for growth and survival of KMT2A rearranged AML cells. Both KMTs have been shown to modulate expression of HOXA cluster genes, albeit for EZH2 this has not been shown in the context of KMT2A rearranged AML, but in other subtypes of AML. We asked what transcriptional effects dual inhibition of DOT1L and EZH2 has in KMT2A rearranged AML. Overall design: Molm14 AML cells were exposed to the DOT1L inhibitor EPZ5676 at 0.16 uM, and the EZH2 inhibitor GSK126 at 0.3 uM for 7 days. Fresh media and compound were supplied on day 4. RNA was isolated using RNeasy (Quiagen) and submitted for RNA-Seq