Agents that target signaling kinases (e.g., JAK1/2) and epigenetic mechanisms (e.g., BET proteins) were shown to result in enhancer reprogramming via newly-marshaled activities of lineage-specific transcriptional regulators which creates the transcriptome/proteome conferring drug tolerant persister/resistance in AML cells33,48,49. The gene discussed is JAK1; the disease is acute myeloid leukemia.