Cell Stem Cell 2021 Jul 12. Epub 2021 Jul 12.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, ON, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, Toronto, ON, Canada. Electronic address:
Current treatments for acute myeloid leukemia (AML) are often ineffective in eliminating leukemic stem cells (LSCs), which perpetuate the disease. Here, we performed a metabolic drug screen to identify LSC-specific vulnerabilities and found that nicotinamide phosphoribosyltransferase (NAMPT) inhibitors selectively killed LSCs, while sparing normal hematopoietic stem and progenitor cells. Treatment with KPT-9274, a NAMPT inhibitor, suppressed the conversion of saturated fatty acids to monounsaturated fatty acids, a reaction catalyzed by the stearoyl-CoA desaturase (SCD) enzyme, resulting in apoptosis of AML cells. Read More