Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia [ATAC-Seq]

A hallmark of acute myeloid leukemia (AML) is the inability of self-renewing malignant cells to mature into a non-dividing terminally differentiated state. To better understand how chromatin factors such as LSD1 interact with metabolic pathways to support the differentiation blockade, we screened a small molecule library to identify druggable substrates that promote myeloid maturation. We found that differentiation caused by LSD1 inhibition is enhanced by combinatorial perturbation of purine nucleotide salvage and de novo lipogenesis pathways. We used ATAC-seq to determine whether the drug combination induces chromatin changes. Overall design: ATAC-seq analysis of non-treated cells at beginning of experiment and of vehicle or drug treated cells after 2 days, with 2 biological replicates per condition.