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CD27‐triggering on primary plasma cell leukaemia cells has anti‐apoptotic effects involving mitogen activated protein kinases
Author(s) -
Guikema Jeroen E. J.,
Vellenga Edo,
Abdulahad Wayel H.,
Hovenga Sjoerd,
Bos Nicolaas A.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04783.x
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , apoptosis , kinase , microbiology and biotechnology , protein kinase a , chemistry , plasma cell , signal transduction , cancer research , biology , immunology , antibody , biochemistry
Summary 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‐ κ B. These findings suggest that, in primary PCL, specific anti‐apoptotic pathways exist that might provide novel therapeutic targets.