National Academy of Sciences, Proceedings of the National Academy of Sciences, 10(111), p. 3805-3810, 2014
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Significance mTOR, a kinase that senses and responds to nutrients, plays critical roles in organogenesis and tumorigenesis. Although mTOR inhibitors have been developed as immunosuppressants and anticancer drugs, it has remained controversial whether such medications contribute to cancer eradication. In addition, mTOR inhibition by chemical inhibitors is complicated because it may not produce predictable inhibition of the mTOR complexes mTORC1 and mTORC2. By using a genetic approach, our study clearly demonstrates that mTORC1, but not mTORC2, is essential for cell cycling of early T-cell progenitors. More importantly, we reveal that loss of mTORC1 efficiently eradicates T-cell acute lymphoblastic leukemia cells, but not myeloid leukemia. Thus, understanding the cell-context–dependent role of mTOR illustrates the potential importance of mTOR signals as therapeutic targets.