DOT1L inhibition is lethal for multiple myeloma due to perturbation of the endoplasmic reticulum stress pathway.

ABSTRACT: The histone 3 lysine 79 (H3K79) methyltransferase (HMT) DOT1L is known to play a critical role for growth and survival of MLL-rearranged leukemia. Serendipitous observations during high-throughput drug screens indicated that the use of DOT1L inhibitors might be expandable to multiple myeloma (MM). Through pharmacologic and genetic experiments, we could validate that DOT1L is essential for growth and viability of a subset of MM cell lines, in line with a recent report from another team. In vivo activity against established MM xenografts was observed with a novel DOT1L inhibitor. In order to understand the molecular mechanism of the dependency in MM, we examined gene expression changes upon DOT1L inhibition in sensitive and insensitive cell lines and discovered that genes belon

SUBMITTER: Dafflon C 

PROVIDER: S-EPMC7082114 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature