PMID- 22958934
OWN - NLM
STAT- MEDLINE
DCOM- 20130529
LR  - 20231120
IS  - 1875-9777 (Electronic)
IS  - 1934-5909 (Print)
IS  - 1875-9777 (Linking)
VI  - 11
IP  - 3
DP  - 2012 Sep 7
TI  - mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked 
      leukemogenesis.
PG  - 429-39
LID - 10.1016/j.stem.2012.06.009 [doi]
AB  - The mechanistic target of rapamycin (mTOR) pathway serves as a key sensor of 
      cellular-energetic state and functions to maintain tissue homeostasis. 
      Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) 
      function and is associated with leukemogenesis. However, the roles of the unique 
      mTOR complexes (mTORCs) in hematopoiesis and leukemogenesis have not been 
      adequately elucidated. We deleted the mTORC1 component, regulatory-associated 
      protein of mTOR (Raptor), in mouse HSCs and its loss causes a nonlethal phenotype 
      characterized by pancytopenia, splenomegaly, and the accumulation of monocytoid 
      cells. Furthermore, Raptor is required for HSC regeneration, and plays largely 
      nonredundant roles with rapamycin-insensitive companion of mTOR (Rictor) in these 
      processes. Ablation of Raptor also significantly extends survival of mice in 
      models of leukemogenesis evoked by Pten deficiency. These data delineate critical 
      roles for mTORC1 in hematopoietic function and leukemogenesis and inform clinical 
      strategies based on chronic mTORC1 inhibition.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Kalaitzidis, Demetrios
AU  - Kalaitzidis D
AD  - Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber 
      Cancer Institute, Harvard Medical School and the Harvard Stem Cell Institute, 
      Boston, MA 02115, USA.
FAU - Sykes, Stephen M
AU  - Sykes SM
FAU - Wang, Zhu
AU  - Wang Z
FAU - Punt, Natalie
AU  - Punt N
FAU - Tang, Yuefeng
AU  - Tang Y
FAU - Ragu, Christine
AU  - Ragu C
FAU - Sinha, Amit U
AU  - Sinha AU
FAU - Lane, Steven W
AU  - Lane SW
FAU - Souza, Amanda L
AU  - Souza AL
FAU - Clish, Clary B
AU  - Clish CB
FAU - Anastasiou, Dimitrios
AU  - Anastasiou D
FAU - Gilliland, D Gary
AU  - Gilliland DG
FAU - Scadden, David T
AU  - Scadden DT
FAU - Guertin, David A
AU  - Guertin DA
FAU - Armstrong, Scott A
AU  - Armstrong SA
LA  - eng
SI  - GEO/GSE32265
GR  - U01 CA105423/CA/NCI NIH HHS/United States
GR  - R01 HL044851/HL/NHLBI NIH HHS/United States
GR  - K01DK092300/DK/NIDDK NIH HHS/United States
GR  - HL097748/HL/NHLBI NIH HHS/United States
GR  - K99 CA158461/CA/NCI NIH HHS/United States
GR  - R00 CA129613/CA/NCI NIH HHS/United States
GR  - P01 CA066996/CA/NCI NIH HHS/United States
GR  - U01 HL100402/HL/NHLBI NIH HHS/United States
GR  - HL097794/HL/NHLBI NIH HHS/United States
GR  - K01 DK092300/DK/NIDDK NIH HHS/United States
GR  - R01 HL097794/HL/NHLBI NIH HHS/United States
GR  - R01 HL097748/HL/NHLBI NIH HHS/United States
GR  - R01 DK050234/DK/NIDDK NIH HHS/United States
GR  - DK050234/DK/NIDDK NIH HHS/United States
GR  - CA66996/CA/NCI NIH HHS/United States
GR  - R00 CA158461/CA/NCI NIH HHS/United States
GR  - DK049216/DK/NIDDK NIH HHS/United States
GR  - HL100402/HL/NHLBI NIH HHS/United States
GR  - CA105423/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Stem Cell
JT  - Cell stem cell
JID - 101311472
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Rptor protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
CIN - Cell Stem Cell. 2012 Sep 7;11(3):281-2. PMID: 22958924
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Carrier Proteins
MH  - Cell Cycle/genetics
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Cell Transformation, Neoplastic/*pathology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation, Leukemic
MH  - *Hematopoiesis/genetics
MH  - Hematopoietic Stem Cell Mobilization
MH  - Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/metabolism/pathology
MH  - Homeostasis
MH  - Leukemia/*enzymology/*pathology
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Multiprotein Complexes/*metabolism
MH  - PTEN Phosphohydrolase/*deficiency/metabolism
MH  - Regulatory-Associated Protein of mTOR
MH  - Survival Analysis
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3743253
MID - NIHMS403146
EDAT- 2012/09/11 06:00
MHDA- 2013/05/31 06:00
PMCR- 2013/09/07
CRDT- 2012/09/11 06:00
PHST- 2011/10/05 00:00 [received]
PHST- 2012/04/10 00:00 [revised]
PHST- 2012/06/08 00:00 [accepted]
PHST- 2012/09/11 06:00 [entrez]
PHST- 2012/09/11 06:00 [pubmed]
PHST- 2013/05/31 06:00 [medline]
PHST- 2013/09/07 00:00 [pmc-release]
AID - S1934-5909(12)00371-2 [pii]
AID - 10.1016/j.stem.2012.06.009 [doi]
PST - ppublish
SO  - Cell Stem Cell. 2012 Sep 7;11(3):429-39. doi: 10.1016/j.stem.2012.06.009.