Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity

Crosstalk between metabolic and survival pathways is critical for cellular homeostasis, but the connectivity between these processes remains poorly defined. We used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of influencing cellular commitment to apoptosis, using sensitization to the BCL-2 inhibitor ABT-199 in BCL-2-dependent acute myeloid leukemia (AML) cell lines as a proxy for apoptotic disposition....