14 research outputs found
Optimizing pharmacists' detection of prescribing errors: Comparison of onâward and central pharmacy services
Acute tubular necrosis (ATN) presenting with an unusually prolonged period of marked polyuria heralded by an abrupt oliguric phase
Effect of prostaglandin E administration in a nephrotoxic and a vasoconstrictor model of acute renal failure
Impact of pharmacist interventions on clinical outcome and cost avoidance in a university teaching hospital
C/EBPa confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative stress-induced ferroptosis in FLT3-mutant leukemia.
While transcription factor C/AAT-enhancer binding protein a (C/EBPa) is critical for normal and leukemic differentiation, its role on cell and metabolic homeostasis is largely unknown in cancer. Here, multi-omics analyses uncovered a coordinated activation of C/EBPa and Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism in vivo and in patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, C/EBPa regulated FASN-SCD axis to promote fatty acid (FA) biosynthesis and desaturation. We further demonstrated that FLT3 or C/EBPa inactivation decreased mono-unsaturated FA incorporation to membrane phospholipids through SCD downregulation. Consequently, SCD inhibition enhanced susceptibility to lipid redox stress that was exploited by combining FLT3 and glutathione peroxidase 4 inhibition to trigger lipid oxidative stress, enhancing ferroptotic death of FLT3-mutant AML cells. Altogether, our study reveals a C/EBPa function in lipid homeostasis and adaptation to redox stress, and a previously unreported vulnerability of FLT3-mutant AML to ferroptosis with promising therapeutic application