PMID- 27030515
OWN - NLM
STAT- MEDLINE
DCOM- 20170602
LR  - 20220727
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 174
IP  - 3
DP  - 2016 Aug
TI  - mTOR Inhibition improves anaemia and reduces organ damage in a murine model of 
      sickle cell disease.
PG  - 461-9
LID - 10.1111/bjh.14057 [doi]
AB  - Mechanistic target of rapamycin (mTOR) has been shown to play an important role 
      in red blood cell physiology, with inhibition of mTOR signalling leading to 
      alterations in erythropoiesis. To determine if mTOR inhibition would improve 
      anaemia in sickle cell disease (SCD), mice with SCD were treated with the dual 
      mTORC1/2 inhibitor, INK128. One week after daily oral drug treatment, erythrocyte 
      count, haemoglobin, and haematocrit were all significantly increased while 
      reticulocyte counts were reduced. These parameters remained stable during 3 weeks 
      of treatment. Similar effects were observed following oral treatment with the 
      mTORC1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle 
      cell erythrocytes in circulation, reduced spleen size, and reduced renal and 
      hepatic iron accumulation in SCD mice. Following middle cerebral artery 
      occlusion, stroke size was reduced in SCD mice treated with sirolimus. In 
      conclusion, mTOR inhibition is protective against anaemia and organ damage in a 
      murine model of SCD.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Wang, Jintao
AU  - Wang J
AD  - Department of Internal Medicine, University of Michigan, Cardiovascular Research 
      Center, Ann Arbor, MI, USA.
FAU - Tran, Jennifer
AU  - Tran J
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Internal Medicine, University of Michigan, Cardiovascular Research 
      Center, Ann Arbor, MI, USA.
FAU - Guo, Chiao
AU  - Guo C
AD  - Department of Internal Medicine, University of Michigan, Cardiovascular Research 
      Center, Ann Arbor, MI, USA.
FAU - Harro, David
AU  - Harro D
AD  - Chemical Pathology, University of Michigan, Ann Arbor, MI, USA.
FAU - Campbell, Andrew D
AU  - Campbell AD
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
FAU - Eitzman, Daniel T
AU  - Eitzman DT
AD  - Department of Internal Medicine, University of Michigan, Cardiovascular Research 
      Center, Ann Arbor, MI, USA.
LA  - eng
GR  - I01 BX002776/BX/BLRD VA/United States
GR  - R01 HL073150/HL/NHLBI NIH HHS/United States
GR  - R01 HL088419/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20160331
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Benzoxazoles)
RN  - 0 (Hemoglobins)
RN  - 0 (Pyrimidines)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - JGH0DF1U03 (sapanisertib)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Anemia/prevention & control
MH  - Anemia, Sickle Cell/complications/*drug therapy
MH  - Animals
MH  - Benzoxazoles/administration & dosage/*pharmacology
MH  - Disease Models, Animal
MH  - Erythrocytes/drug effects
MH  - Hematocrit
MH  - Hemoglobins
MH  - Mice
MH  - Pyrimidines/administration & dosage/*pharmacology
MH  - Sirolimus/*therapeutic use
MH  - Splenomegaly/drug therapy/prevention & control
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC4959967
MID - NIHMS765903
OTO - NOTNLM
OT  - anaemia
OT  - mechanistic target of rapamycin
OT  - sickle cell disease
OT  - sirolimus
OT  - stroke
EDAT- 2016/04/01 06:00
MHDA- 2017/06/03 06:00
PMCR- 2016/09/01
CRDT- 2016/04/01 06:00
PHST- 2015/11/23 00:00 [received]
PHST- 2016/01/19 00:00 [accepted]
PHST- 2016/04/01 06:00 [entrez]
PHST- 2016/04/01 06:00 [pubmed]
PHST- 2017/06/03 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - 10.1111/bjh.14057 [doi]
PST - ppublish
SO  - Br J Haematol. 2016 Aug;174(3):461-9. doi: 10.1111/bjh.14057. Epub 2016 Mar 31.