title: [Roles of mTORC1 in acute myeloid leukemia].
abstract: Constitutive activation of mTOR is associated with acceleration of leukemia development. However, mTORC1 functions in established leukemia are unclear. We evaluated the role of mTORC1 in mouse acute myeloid leukemia (AML) cells using a murine model of conditional deletion of Raptor, an essential component of mTORC1, and an MLL-AF9-driven leukemia model. mTORC1 is essential for leukemia initiation, but a subset of AML cells with undifferentiated phenotypes survived long-term in the absence of mTORC1 activity. Our study demonstrated AML cells lacking mTORC1 activity to be capable of self-renewal as AML stem cells. This review will summarize our study on the roles of mTORC1 in AML, and discuss potential benefits and risks of mTORC2 inhibition and the potential use of mTOR inhibitors as AML therapy.
authors.affiliation: Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshii
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D051788:Myeloid-Lymphoid Leukemia Protein; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases