@article {1574695,
	title = {Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers},
	journal = {Blood},
	volume = {136},
	number = {11},
	year = {2020},
	month = {2020 Sep 10},
	pages = {1303-1316},
	abstract = {Metabolic alterations in cancer represent convergent effects of oncogenic mutations. We hypothesized that a metabolism-restricted genetic screen, comparing normal primary mouse hematopoietic cells and their malignant counterparts in an ex vivo system mimicking the bone marrow microenvironment, would define distinctive vulnerabilities in acute myeloid leukemia (AML). Leukemic cells, but not their normal myeloid counterparts, depended on the aldehyde dehydrogenase 3a2 (Aldh3a2) enzyme that oxidizes long-chain aliphatic aldehydes to prevent cellular oxidative damage. Aldehydes are by-products of increased oxidative phosphorylation and nucleotide synthesis in cancer and are generated from lipid peroxides underlying the non-caspase-dependent form of cell death, ferroptosis. Leukemic cell dependence on Aldh3a2 was seen across multiple mouse and human myeloid leukemias. Aldh3a2 inhibition was synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition; GPX4 inhibition is a known trigger of ferroptosis that by itself minimally affects AML cells. Inhibiting Aldh3a2 provides a therapeutic opportunity and a unique synthetic lethality to exploit the distinctive metabolic state of malignant cells.},
	issn = {1528-0020},
	doi = {10.1182/blood.2019001808},
	author = {Yusuf, Rushdia Zareen and Saez, Borja and Sharda, Azeem and van Gastel, Nick and Yu, Vionnie W C and Baryawno, Ninib and Scadden, Elizabeth W and Acharya, Sanket and Chattophadhyay, Shrikanta and Huang, Cherrie and Viswanathan, Vasanthi and S{\textquoteright}aulis, Dana and Cobert, Julien and Sykes, David B and Keibler, Mark A and Das, Sudeshna and Hutchinson, John N and Churchill, Michael and Mukherjee, Siddhartha and Lee, Dongjun and Mercier, Francois and Doench, John and Bullinger, Lars and Logan, David J and Schreiber, Stuart and Stephanopoulos, Gregory and Rizzo, William B and Scadden, David T}
}
