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
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"mTORC1 is essential for leukemia pr..." refers background in this paper
...Although mTORC1 has been assumed to function in growth and metabolism of most cell types, previous studies of mice lacking Raptor only in adipocytes or muscle suggest that mTORC1 may have distinct functions in homeostasis depending on the tissue (8, 9)....
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555 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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...Because AML stem cells likely originate from myeloid progenitors, the two types of cells may share the property of mTORC1 dependency (22)....
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...macrophage progenitors (GMPs), rather than to HSCs (22)....
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...are associated with stem cell phenotypes in AML is similar to that in HSCs or embryonic stem cells (18, 22, 23)....
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544 citations
"mTORC1 is essential for leukemia pr..." refers methods 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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...To create a representative AML model, we first inserted the MLL-AF9 fusion gene (17, 18, 21) into K+S+L– cells isolated from Raptorfl/fl, Raptor+/+CreER, or Raptorfl/flCreER mice by using retrovirus-mediated transfer....
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464 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Although mTORC1 has been assumed to function in growth and metabolism of most cell types, previous studies of mice lacking Raptor only in adipocytes or muscle suggest that mTORC1 may have distinct functions in homeostasis depending on the tissue (8, 9)....
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