mTORC1 is essential for leukemia propagation but not stem cell self-renewal
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Cites background from "mTORC1 is essential for leukemia pr..."
...Phosphorylation of p62 and induction of Nqo1 both decreased upon As(III) exposure in MEFs lacking Raptor (Hoshii et al., 2012), a component of the mTORC1 complex (Figures S2B and S2C)....
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Cites background from "mTORC1 is essential for leukemia pr..."
...Conversely, the deletion of the MTORC1 component RAPTOR, therefore theoretically causing an increase in autophagy, results in a decrease of this myeloid population.(91) However, it remains to be shown definitively that loss or gain of autophagy contributes to this phenotype, as MTOR inhibition signals for many other important cellular functions such as inhibition of protein translation, mitochondrial biogenesis, cell growth, motility and proliferation....
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Cites background from "mTORC1 is essential for leukemia pr..."
...Recently, it was shown in a raptor deficiency mouse model thatmTORC1 inactivation induces apoptosis in differentiated leukemic cells and maintains immature leukemic cells with leukemia initiation potential in a dormant state, underlying the critical role of mTORC1 in leukemia.(4) In vitro, in primary AML cells, mTORC1 inhibition with rapamycin has cytostatic effects but does not induce apoptosis,(2-5) mainly because it does not inhibit 4E-BP1 phosphorylation on ser65....
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References
1,002 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...of mTORC1, including Raptor, 4E-BP1/2, AKTS1 (also known as PRAS40), and LARP1 (26, 27)....
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...Among these molecules, there were several known downstream targets of mTORC1, including Raptor, 4E-BP1/2, AKTS1 (also known as PRAS40), and LARP1 (26, 27)....
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...Feedback activation of the PI3K/AKT pathway is triggered by inhibition of Grb10 and/or activation of IRS after acute mTORC1 inactivation (26, 27)....
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...org Volume 122 Number 6 June 2012 rapamycin and ATP-competitive mTOR inhibitors (26, 27)....
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963 citations
829 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Previous studies demonstrated that mTORC1 activity plays critical roles in cell proliferation in embryonic fibroblasts and cell lines (45, 46)....
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820 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Pten deficiency in hematopoietic cells promotes myeloproliferative disease followed by development of leukemia (12, 14, 15)....
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815 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...This is illustrated by the case of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors (37, 38)....
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