Document Detail


CD27-triggering on primary plasma cell leukaemia cells has anti-apoptotic effects involving mitogen activated protein kinases.
MedLine Citation:
PMID:  14717776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was set out to assess the functional properties of CD27 expressed on PCL plasma cells by triggering with its ligand CD70. Using CD27-expressing purified plasma cells from a PCL patient we demonstrated that CD27-triggering modestly inhibited spontaneous and dexamethasone-induced apoptosis. In vitro stimulation and Western blotting showed that activation of p38 and extracellular-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPK) was associated with CD27-mediated signal transduction. Specific inhibition of p38 and ERK1/2 MAPK abolished the anti-apoptotic effects of CD27-triggering. Interestingly, simultaneous inhibition of p38 and ERK1/2 strongly sensitized PCL cells for dexamethasone-induced apoptosis. Finally, in dexamethasone-treated PCL cells, CD27-triggering was associated with persistent DNA-binding activity of activator protein 1 (AP-1) but not of nuclear factor-kappaB. These findings suggest that, in primary PCL, specific anti-apoptotic pathways exist that might provide novel therapeutic targets.
Authors:
Jeroen E J Guikema; Edo Vellenga; Wayel H Abdulahad; Sjoerd Hovenga; Nicolaas A Bos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of haematology     Volume:  124     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-13     Completed Date:  2004-04-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  299-308     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Section Histology and Immunology, Faculty of Medical Sciences, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD27 / immunology*
Apoptosis / drug effects*
Blotting, Western / methods
Butadienes / pharmacology
Dexamethasone / pharmacology
Electrophoretic Mobility Shift Assay
Enzyme Inhibitors / pharmacology
Glucocorticoids / pharmacology
Humans
Imidazoles / pharmacology
Leukemia, Plasma Cell / immunology*
MAP Kinase Signaling System*
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism
Nitriles / pharmacology
Pyridines / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Statistics, Nonparametric
Transcription Factor AP-1 / metabolism
Tumor Cells, Cultured
p38 Mitogen-Activated Protein Kinases
Chemical
Reg. No./Substance:
0/Antigens, CD27; 0/Butadienes; 0/Enzyme Inhibitors; 0/Glucocorticoids; 0/Imidazoles; 0/Nitriles; 0/Pyridines; 0/SB 203580; 0/Transcription Factor AP-1; 0/U 0126; 50-02-2/Dexamethasone; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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