PMID- 24778454
OWN - NLM
STAT- MEDLINE
DCOM- 20150121
LR  - 20211021
IS  - 1757-4684 (Electronic)
IS  - 1757-4676 (Print)
IS  - 1757-4676 (Linking)
VI  - 6
IP  - 6
DP  - 2014 Jun
TI  - Interleukin-18 produced by bone marrow-derived stromal cells supports T-cell 
      acute leukaemia progression.
PG  - 821-34
LID - 10.1002/emmm.201303286 [doi]
AB  - Development of novel therapies is critical for T-cell acute leukaemia (T-ALL). 
      Here, we investigated the effect of inhibiting the MAPK/MEK/ERK pathway on T-ALL 
      cell growth. Unexpectedly, MEK inhibitors (MEKi) enhanced growth of 70% of human 
      T-ALL cell samples cultured on stromal cells independently of NOTCH activation 
      and maintained their ability to propagate in vivo. Similar results were obtained 
      when T-ALL cells were cultured with ERK1/2-knockdown stromal cells or with 
      conditioned medium from MEKi-treated stromal cells. Microarray analysis 
      identified interleukin 18 (IL-18) as transcriptionally up-regulated in 
      MEKi-treated MS5 cells. Recombinant IL-18 promoted T-ALL growth in vitro, whereas 
      the loss of function of IL-18 receptor in T-ALL blast cells decreased blast 
      proliferation in vitro and in NSG mice. The NFKB pathway that is downstream to 
      IL-18R was activated by IL-18 in blast cells. IL-18 circulating levels were 
      increased in T-ALL-xenografted mice and also in T-ALL patients in comparison with 
      controls. This study uncovers a novel role of the pro-inflammatory cytokine IL-18 
      and outlines the microenvironment involvement in human T-ALL development.
CI  - (c) 2014 The Authors. Published under the terms of the CC BY 4.0 license.
FAU - Uzan, Benjamin
AU  - Uzan B
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Poglio, Sandrine
AU  - Poglio S
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Gerby, Bastien
AU  - Gerby B
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Wu, Ching-Lien
AU  - Wu CL
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Gross, Julia
AU  - Gross J
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Armstrong, Florence
AU  - Armstrong F
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Calvo, Julien
AU  - Calvo J
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Cahu, Xavier
AU  - Cahu X
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France.
FAU - Deswarte, Caroline
AU  - Deswarte C
AD  - Service D'hematologie Pediatrique, Assistance Publique - Hopitaux de Paris 
      Hopital A. Trousseau, Paris, France.
FAU - Dumont, Florent
AU  - Dumont F
AD  - INSERM U1016 Institut Cochin, Paris, France CNRS UMR8104, Paris, France 
      Universite Paris Descartes Sorbonne Paris Cite, Paris, France.
FAU - Passaro, Diana
AU  - Passaro D
AD  - Institut Curie Centre Universitaire, Orsay, France CNRS UMR 3306, Orsay, France 
      Institut National de la Sante et de la Recherche Medicale U1005, Orsay, France.
FAU - Besnard-Guerin, Corinne
AU  - Besnard-Guerin C
AD  - INSERM U1016 Institut Cochin, Paris, France CNRS UMR8104, Paris, France 
      Universite Paris Descartes Sorbonne Paris Cite, Paris, France.
FAU - Leblanc, Thierry
AU  - Leblanc T
AD  - Service D'hematologie Pediatrique, Assistance Publique - Hopitaux de Paris 
      Hopital Robert Debre, Paris, France.
FAU - Baruchel, Andre
AU  - Baruchel A
AD  - Service D'hematologie Pediatrique, Assistance Publique - Hopitaux de Paris 
      Hopital Robert Debre, Paris, France.
FAU - Landman-Parker, Judith
AU  - Landman-Parker J
AD  - Service D'hematologie Pediatrique, Assistance Publique - Hopitaux de Paris 
      Hopital A. Trousseau, Paris, France.
FAU - Ballerini, Paola
AU  - Ballerini P
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France Service D'hematologie Pediatrique, 
      Assistance Publique - Hopitaux de Paris Hopital A. Trousseau, Paris, France.
FAU - Baud, Veronique
AU  - Baud V
AD  - INSERM U1016 Institut Cochin, Paris, France CNRS UMR8104, Paris, France 
      Universite Paris Descartes Sorbonne Paris Cite, Paris, France.
FAU - Ghysdael, Jacques
AU  - Ghysdael J
AD  - Institut Curie Centre Universitaire, Orsay, France CNRS UMR 3306, Orsay, France 
      Institut National de la Sante et de la Recherche Medicale U1005, Orsay, France.
FAU - Baleydier, Frederic
AU  - Baleydier F
AD  - Institut d'Hematologie et Oncologie Pediatrique Hospices Civils de Lyon et 
      Universite Claude Bernard, Lyon, France.
FAU - Porteu, Francoise
AU  - Porteu F
AD  - INSERM U1016 Institut Cochin, Paris, France CNRS UMR8104, Paris, France 
      Universite Paris Descartes Sorbonne Paris Cite, Paris, France.
FAU - Pflumio, Francoise
AU  - Pflumio F
AD  - Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA) 
      DSV-IRCM-SCSR-LSHL Equipe Labellisee Ligue Contre le Cancer UMR 967, 
      Fontenay-aux-Roses, France INSERM U967, Fontenay-aux-Roses, France Universite 
      Paris Diderot Sorbonne Paris Cite UMR 967, Fontenay-aux-Roses, France Universite 
      Paris-Sud UMR 967, Fontenay-aux-Roses, France francoise.pflumio@cea.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140406
PL  - England
TA  - EMBO Mol Med
JT  - EMBO molecular medicine
JID - 101487380
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/metabolism/pathology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Gene Expression Regulation, Leukemic
MH  - Gene Silencing
MH  - Humans
MH  - Interleukin-18/blood/genetics/*immunology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Precursor T-Cell Lymphoblastic 
      Leukemia-Lymphoma/blood/genetics/*immunology/pathology
MH  - Stromal Cells/cytology/*immunology/metabolism/pathology
MH  - T-Lymphocytes/immunology/metabolism/pathology
PMC - PMC4203358
OTO - NOTNLM
OT  - IL-18
OT  - T-ALL
OT  - inflammation
OT  - stromal cells
EDAT- 2014/04/30 06:00
MHDA- 2015/01/22 06:00
PMCR- 2014/06/01
CRDT- 2014/04/30 06:00
PHST- 2014/04/30 06:00 [entrez]
PHST- 2014/04/30 06:00 [pubmed]
PHST- 2015/01/22 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - emmm.201303286 [pii]
AID - 10.1002/emmm.201303286 [doi]
PST - ppublish
SO  - EMBO Mol Med. 2014 Jun;6(6):821-34. doi: 10.1002/emmm.201303286. Epub 2014 Apr 6.