mTORC1 is essential for leukemia propagation but not stem cell self-renewal
Citations
2,194 citations
824 citations
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)....
[...]
262 citations
255 citations
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....
[...]
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....
[...]
References
462 citations
369 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Although previous studies reported that inhibition of 4E-BP phosphorylation is associated with the induction of apoptosis in tumors (39, 40), it was assumed that other molecules downstream of mTORC1 cooperatively contribute to AML propagation....
[...]
337 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)....
[...]
336 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...are associated with stem cell phenotypes in AML is similar to that in HSCs or embryonic stem cells (18, 22, 23)....
[...]
320 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...In addition, mTORC1 regulates mitochondrial biogenesis (2, 3) and autophagy (4)....
[...]