PMID- 30274374
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20190107
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 10
DP  - 2018 Sep 30
TI  - Implication and Regulation of AMPK during Physiological and Pathological Myeloid 
      Differentiation.
LID - 10.3390/ijms19102991 [doi]
LID - 2991
AB  - AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine kinase 
      consisting of the arrangement of various alpha beta, and gammaisoforms that are expressed 
      differently depending on the tissue or the cell lineage. AMPK is one of the major 
      sensors of energy status in mammalian cells and as such plays essential roles in 
      the regulation of cellular homeostasis, metabolism, cell growth, differentiation, 
      apoptosis, and autophagy. AMPK is activated by two upstream kinases, the tumor 
      suppressor liver kinase B1 (LKB1) and the calcium/calmodulin-dependent protein 
      kinase kinase 2 (CAMKK2) through phosphorylation of the kinase on Thr172, leading 
      to its activation. In addition, AMPK inhibits the mTOR pathway through 
      phosphorylation and activation of tuberous sclerosis protein 2 (TSC2) and causes 
      direct activation of unc-51-like autophagy activating kinase 1 (ULK1) via 
      phosphorylation of Ser555, thus promoting initiation of autophagy. Although it is 
      well established that AMPK can control the differentiation of different cell 
      lineages, including hematopoietic stem cells (HSCs), progenitors, and mature 
      hematopoietic cells, the role of AMPK regarding myeloid cell differentiation is 
      less documented. The differentiation of monocytes into macrophages triggered by 
      colony stimulating factor 1 (CSF-1), a process during which both caspase 
      activation (independently of apoptosis induction) and AMPK-dependent stimulation 
      of autophagy are necessary, is one noticeable example of the involvement of AMPK 
      in the physiological differentiation of myeloid cells. The present review focuses 
      on the role of AMPK in the regulation of the physiological and pathological 
      differentiation of myeloid cells. The mechanisms of autophagy induction by AMPK 
      will also be addressed, as autophagy has been shown to be important for 
      differentiation of hematopoietic cells. In addition, myeloid malignancies 
      (myeloid leukemia or dysplasia) are characterized by profound defects in the 
      establishment of proper differentiation programs. Reinduction of a normal 
      differentiation process in myeloid malignancies has thus emerged as a valuable 
      and promising therapeutic strategy. As AMPK seems to exert a key role in the 
      differentiation of myeloid cells, notably through induction of autophagy, we will 
      also discuss the potential to target this pathway as a pro-differentiating and 
      anti-leukemic strategy in myeloid malignancies.
FAU - Jacquel, Arnaud
AU  - Jacquel A
AD  - Universite Cote d'Azur, C3M Inserm U1065, 06204 Nice, France. jacquel@unice.fr.
AD  - Equipe Labellisee par la Fondation ARC, 94803 Villejuif, France. 
      jacquel@unice.fr.
FAU - Luciano, Frederic
AU  - Luciano F
AD  - Universite Cote d'Azur, C3M Inserm U1065, 06204 Nice, France. fluciano@unice.fr.
AD  - Equipe Labellisee par la Fondation ARC, 94803 Villejuif, France. 
      fluciano@unice.fr.
FAU - Robert, Guillaume
AU  - Robert G
AD  - Universite Cote d'Azur, C3M Inserm U1065, 06204 Nice, France. robertg@unice.fr.
AD  - Equipe Labellisee par la Fondation ARC, 94803 Villejuif, France. 
      robertg@unice.fr.
FAU - Auberger, Patrick
AU  - Auberger P
AD  - Universite Cote d'Azur, C3M Inserm U1065, 06204 Nice, France. auberger@unice.fr.
AD  - Equipe Labellisee par la Fondation ARC, 94803 Villejuif, France. 
      auberger@unice.fr.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180930
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/chemistry/*metabolism
MH  - Animals
MH  - *Cell Differentiation
MH  - Enzyme Activation
MH  - Hematologic Neoplasms/pathology
MH  - Hematopoietic Stem Cells/pathology
MH  - Humans
MH  - Myeloid Cells/*enzymology/*pathology
PMC - PMC6213055
OTO - NOTNLM
OT  - AML
OT  - AMPK
OT  - CML
OT  - CMML
OT  - MDS
OT  - autophagy
OT  - differentiation
OT  - macrophages
OT  - monocytes
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/10/03 06:00
MHDA- 2019/01/08 06:00
PMCR- 2018/10/01
CRDT- 2018/10/03 06:00
PHST- 2018/09/06 00:00 [received]
PHST- 2018/09/27 00:00 [revised]
PHST- 2018/09/28 00:00 [accepted]
PHST- 2018/10/03 06:00 [entrez]
PHST- 2018/10/03 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - ijms19102991 [pii]
AID - ijms-19-02991 [pii]
AID - 10.3390/ijms19102991 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Sep 30;19(10):2991. doi: 10.3390/ijms19102991.