mTORC1 is essential for leukemia propagation but not stem cell self-renewal
Citations
219 citations
165 citations
Cites methods from "mTORC1 is essential for leukemia pr..."
...The raptor flox mouse model has been described,((8)) and the mTOR flox mouse will be described elsewhere (Hoshii et al....
[...]
155 citations
150 citations
Cites background from "mTORC1 is essential for leukemia pr..."
...In order to investigate the critical role of Raptor in established acute myeloid leukemia (AML), Raptor, Raptor/CreER and Raptor/CreER AML mice were generated by transplantation of theMLL-AF9 fusion genemodified hematopoietic progenitor cells from Raptor, Raptor/CreER and Raptor/CreER mice into lethally irradiated syngeneic recipients [44]....
[...]
...Interestingly, although loss of Raptor significantly inhibited AML stem cell initiation, the self-renewal ability for these cells was not affected [44], indicating that mTORC1 activity is essential for AML propagation but not AML stem cell self-renewal....
[...]
...Notably, a tamoxifen (TAM)-inducible conditional Raptor KOmouse model (Raptor/CreER) was generated in 2012, where depletion of Raptor in adult mice with TAM in all tissues caused body weight loss anddeathwithin 17 days,with impairment of granulocyte and B cell development in bone marrow [44]....
[...]
...Notably, further analyses of these AML mouse models revealed that Raptor deletion remarkably impaired AML progression owing to an increased induction of cellular apoptosis [44]....
[...]
135 citations
Cites background from "mTORC1 is essential for leukemia pr..."
...Activation of AKT, an upstream regulator of MTOR, decreases autophagy in HSCs and promotes myeloid proliferation,(32) whereas deletion of Rptor/Raptor (regulatory-associated protein of MTOR, complex 1), encoding a component of MTORC1 (MTOR complex 1), enhances autophagy and decreases this myeloid cell population (Table 1).(33) Moreover, HSC self-renewal can be restored by treatment with antioxidants or rapamycin....
[...]
References
8,999 citations
2,902 citations
"mTORC1 is essential for leukemia pr..." refers result in this paper
...Although mTORC1 reportedly controls cell size (cell growth) (34), we did not observe a decrease in the size of our Raptor-deficient AML cells (Figure 6B), and we found that the amount of protein per cell was comparable in control and Raptor-deficient AML stem cells (Figure 6, C and D)....
[...]
2,621 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...We found that Raptor deficiency did not affect the expression level of Rictor, an essential component of mTORC2, but it is possible that long-term inactivation of mTORC1 in Raptordeficient AML cells affects the assembly and activity of mTORC2, leading to inhibition of AKT, in the same manner as prolonged rapamycin treatment (49)....
[...]
...On the other hand, prolonged rapamycin treatment is reported to suppress AKT via the disassembly of the mTORC2 complex in certain cell types (49)....
[...]
2,423 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-...
[...]
2,328 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...These target molecules control cell growth (size) and proliferation by modifying protein translation (1)....
[...]