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
2,194 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Deficiency in Pten, a negative regulator of PI3K/AKT signaling, also impairs the quiescence of HSCs, leading to their depletion....
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...Thus, it is unclear how mTORC1 contributes to the control of growth, proliferation, survival, and differentiation under physiological conditions. mTORC1 dysregulation promotes leukemogenesis and depletes HSCs (10–14)....
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...both HSCs and leukemia stem cells (CSCs in leukemia), leading to the idea that leukemia stem cells may originate from HSCs (16)....
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...A recent study using a large number of primary human AML patient samples indicated that human AML stem cells are immunophenotypically similar to progenitors, including lymphoid-primed multipotential progenitors and granulocytemacrophage progenitors (GMPs), rather than to HSCs (22)....
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...Previous studies have suggested that common mechanisms regulate stem cell properties (stemness) in both HSCs and leukemia stem cells (CSCs in leukemia), leading to the idea that leukemia stem cells may originate from HSCs (16)....
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"mTORC1 is essential for leukemia pr..." refers methods in this paper
...Mice with the Raptorfl allele were crossed with Rosa26-CreERT2 mice (52) obtained from Tyler Jacks (Massachusetts Institute of Tech-...
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1,669 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...It has been reported that mTORC1 inhibition activates autophagy, a protein degradation system, to generate energy for survival under conditions of stress or starvation (4)....
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...In addition, mTORC1 regulates mitochondrial biogenesis (2, 3) and autophagy (4)....
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1,601 citations