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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238 citations
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
787 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Although S6 and eEF2K are substrates of p70S6K, it was also reported that p90 RSK can phosphorylate these proteins (28, 30)....
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784 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...org Volume 122 Number 6 June 2012 (32, 33), neither Raptor deficiency nor rapamycin resulted in hyperphosphorylation of AKT (S473) (Figure 6A and Supplemental Fig-...
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784 citations
"mTORC1 is essential for leukemia pr..." refers background or result in this paper
...blasts (Supplemental Figure 1E), which is consistent with previous reports showing that 4E-BP1 is a rapamycin-insensitive mTORC1 target (24, 25)....
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...However, 4E-BP1, a direct target of mTORC1, is reportedly a rapamycin-insensitive substrate (24, 25)....
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...the phosphorylation of 4E-BP1, which is consistent with previous reports (24, 25)....
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772 citations
726 citations
"mTORC1 is essential for leukemia pr..." refers background or result in this paper
...Previous reports on this AML model have indicated that c-Kit marks undifferentiated AML cells (17, 18, 31)....
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...on this AML model have shown that AML stem cells are highly enriched in the c-Kit+Gr-1– (K+G–) population (31)....
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