PMID- 23778311
OWN - NLM
STAT- MEDLINE
DCOM- 20140306
LR  - 20211021
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 28
IP  - 1
DP  - 2014 Jan
TI  - Multifaceted roles of GSK-3 and Wnt/beta-catenin in hematopoiesis and 
      leukemogenesis: opportunities for therapeutic intervention.
PG  - 15-33
LID - 10.1038/leu.2013.184 [doi]
AB  - Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex 
      array of critical cellular processes. It was initially identified in rat skeletal 
      muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen 
      synthase. This versatile protein is involved in numerous signaling pathways that 
      influence metabolism, embryogenesis, differentiation, migration, cell cycle 
      progression and survival. Recently, GSK-3 has been implicated in leukemia stem 
      cell pathophysiology and may be an appropriate target for its eradication. In 
      this review, we will discuss the roles that GSK-3 plays in hematopoiesis and 
      leukemogenesis as how this pivotal kinase can interact with multiple signaling 
      pathways such as: Wnt/beta-catenin, phosphoinositide 3-kinase (PI3K)/phosphatase and 
      tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), 
      Ras/Raf/MEK/extracellular signal-regulated kinase (ERK), Notch and others. 
      Moreover, we will discuss how targeting GSK-3 and these other pathways can 
      improve leukemia therapy and may overcome therapeutic resistance. In summary, 
      GSK-3 is a crucial regulatory kinase interacting with multiple pathways to 
      control various physiological processes, as well as leukemia stem cells, leukemia 
      progression and therapeutic resistance. GSK-3 and Wnt are clearly intriguing 
      therapeutic targets.
FAU - McCubrey, J A
AU  - McCubrey JA
AD  - Department of Microbiology and Immunology, Brody School of Medicine at East 
      Carolina University, Greenville, NC, USA.
FAU - Steelman, L S
AU  - Steelman LS
AD  - Department of Microbiology and Immunology, Brody School of Medicine at East 
      Carolina University, Greenville, NC, USA.
FAU - Bertrand, F E
AU  - Bertrand FE
AD  - Department of Oncology, Brody School of Medicine at East Carolina University, 
      Greenville, NC, USA.
FAU - Davis, N M
AU  - Davis NM
AD  - Department of Microbiology and Immunology, Brody School of Medicine at East 
      Carolina University, Greenville, NC, USA.
FAU - Abrams, S L
AU  - Abrams SL
AD  - Department of Microbiology and Immunology, Brody School of Medicine at East 
      Carolina University, Greenville, NC, USA.
FAU - Montalto, G
AU  - Montalto G
AD  - Biomedical Department of Internal Medicine and Specialties, University of 
      Palermo, Palermo, Italy.
FAU - D'Assoro, A B
AU  - D'Assoro AB
AD  - Department of Biochemistry and Molecular Biology, Mayo Clinic College of 
      Medicine, Rochester, MN, USA.
FAU - Libra, M
AU  - Libra M
AD  - Department of Bio-Medical Sciences, University of Catania, Catania, Italy.
FAU - Nicoletti, F
AU  - Nicoletti F
AD  - Department of Bio-Medical Sciences, University of Catania, Catania, Italy.
FAU - Maestro, R
AU  - Maestro R
AD  - Experimental Oncology 1, CRO IRCCS, National Cancer Institute, Aviano, Italy.
FAU - Basecke, J
AU  - Basecke J
AD  - 1] Department of Medicine, University of Gottingen, Gottingen, Germany [2] 
      Sanct-Josef-Hospital Cloppenburg, Department of Hematology and Oncology, 
      Cloppenburg, Germany.
FAU - Cocco, L
AU  - Cocco L
AD  - Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, 
      Bologna, Italy.
FAU - Cervello, M
AU  - Cervello M
AD  - Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia 
      Molecolare 'Alberto Monroy', Palermo, Italy.
FAU - Martelli, A M
AU  - Martelli AM
AD  - 1] Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, 
      Bologna, Italy [2] Institute of Molecular Genetics, National Research 
      Council-IOR, Bologna, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130619
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - *Carcinogenesis
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - *Hematopoiesis
MH  - Humans
MH  - Leukemia/enzymology/metabolism/*pathology/therapy
MH  - Wnt Proteins/*metabolism
MH  - beta Catenin/*metabolism
PMC - PMC3887408
EDAT- 2013/06/20 06:00
MHDA- 2014/03/07 06:00
CRDT- 2013/06/20 06:00
PHST- 2013/05/07 00:00 [received]
PHST- 2013/06/08 00:00 [revised]
PHST- 2013/06/11 00:00 [accepted]
PHST- 2013/06/20 06:00 [entrez]
PHST- 2013/06/20 06:00 [pubmed]
PHST- 2014/03/07 06:00 [medline]
AID - leu2013184 [pii]
AID - 10.1038/leu.2013.184 [doi]
PST - ppublish
SO  - Leukemia. 2014 Jan;28(1):15-33. doi: 10.1038/leu.2013.184. Epub 2013 Jun 19.