LSD1 inhibition exerts its antileukemic effect by recommissioning PU.1- and C/EBPα-dependent enhancers in AML.

ABSTRACT: Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine-specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML. We performed a comparative assessment of chromatin dynamics during the treatment of mixed lineage leukemia (MLL)-AF9-driven murine leukemias and MLL-rearranged patie

SUBMITTER: Cusan M 

PROVIDER: S-EPMC5897868 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature