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Expression of ZAP70 in chronic lymphocytic leukaemia activates NF-κB signalling

Valerie Pede UGent, Ans Rombout, JOLIEN VERMEIRE, Evelien Naessens UGent, Hanne Vanderstraeten, Jan Philippé UGent and Bruno Verhasselt UGent (2013) BRITISH JOURNAL OF HAEMATOLOGY. 163(5). p.621-630
abstract
Chronic lymphocytic leukaemia (CLL) is a disease with a highly variable prognosis. The clinical course can however be predicted thanks to prognostic markers. Poor prognosis is associated with expression of a B cell receptor (BCR) from unmutated immunoglobulin variable heavy-chain genes (IGHV) and expression of zeta-associated protein of 70kDa (ZAP70). The reason why ZAP70 expression is associated with poor prognosis and whether the protein has a direct pathogenic function is at present unknown. By transfer of ZAP70 to CLL cells, we show here that expression of ZAP70 in CLL cells leads to increased expression of the nuclear factor (NF)-B target genes interleukin-1 (IL1B), IL6 and IL8 upon BCR triggering. This could be blocked by inhibition of NF-B signalling through inhibition of IB kinases (IKK). Transcriptome analysis identified a NF-B RELA signature imposed by ZAP70 expression in BCR-stimulated CLL cells. We conclude that ZAP70 acts directly as an amplifier of NF-B signalling in CLL cells which could be an underlying mechanism for its association with poor prognosis and which may represent a therapeutic target.
Please use this url to cite or link to this publication:
author
organization
alternative title
Expression of ZAP70 in chronic lymphocytic leukaemia activates NF-kappa B signalling
year
type
journalArticle (original)
publication status
published
subject
keyword
B-cell receptor, nuclear factor-B, zeta-associated protein of 70, chronic lymphocytic leukaemia, MESSENGER-RNA EXPRESSION, CELL-RECEPTOR, ZAP-70 EXPRESSION, ANTIGEN-RECEPTOR, GENE-EXPRESSION, DISEASE PROGRESSION, PROGNOSTIC MARKERS, THERAPEUTIC TARGET, CD38 EXPRESSION, MUTATION STATUS
journal title
BRITISH JOURNAL OF HAEMATOLOGY
Br. J. Haematol.
volume
163
issue
5
pages
621 - 630
Web of Science type
Article
Web of Science id
000326807400010
JCR category
HEMATOLOGY
JCR impact factor
4.959 (2013)
JCR rank
11/68 (2013)
JCR quartile
1 (2013)
ISSN
0007-1048
DOI
10.1111/bjh.12588
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
4283681
handle
http://hdl.handle.net/1854/LU-4283681
date created
2014-02-08 14:51:32
date last changed
2016-12-19 15:43:14
@article{4283681,
  abstract     = {Chronic lymphocytic leukaemia (CLL) is a disease with a highly variable prognosis. The clinical course can however be predicted thanks to prognostic markers. Poor prognosis is associated with expression of a B cell receptor (BCR) from unmutated immunoglobulin variable heavy-chain genes (IGHV) and expression of zeta-associated protein of 70kDa (ZAP70). The reason why ZAP70 expression is associated with poor prognosis and whether the protein has a direct pathogenic function is at present unknown. By transfer of ZAP70 to CLL cells, we show here that expression of ZAP70 in CLL cells leads to increased expression of the nuclear factor (NF)-B target genes interleukin-1 (IL1B), IL6 and IL8 upon BCR triggering. This could be blocked by inhibition of NF-B signalling through inhibition of IB kinases (IKK). Transcriptome analysis identified a NF-B RELA signature imposed by ZAP70 expression in BCR-stimulated CLL cells. We conclude that ZAP70 acts directly as an amplifier of NF-B signalling in CLL cells which could be an underlying mechanism for its association with poor prognosis and which may represent a therapeutic target.},
  author       = {Pede, Valerie and Rombout, Ans and VERMEIRE, JOLIEN and Naessens, Evelien and Vanderstraeten, Hanne and Philipp{\'e}, Jan and Verhasselt, Bruno},
  issn         = {0007-1048},
  journal      = {BRITISH JOURNAL OF HAEMATOLOGY},
  keyword      = {B-cell receptor,nuclear factor-B,zeta-associated protein of 70,chronic lymphocytic leukaemia,MESSENGER-RNA EXPRESSION,CELL-RECEPTOR,ZAP-70 EXPRESSION,ANTIGEN-RECEPTOR,GENE-EXPRESSION,DISEASE PROGRESSION,PROGNOSTIC MARKERS,THERAPEUTIC TARGET,CD38 EXPRESSION,MUTATION STATUS},
  language     = {eng},
  number       = {5},
  pages        = {621--630},
  title        = {Expression of ZAP70 in chronic lymphocytic leukaemia activates NF-\ensuremath{\kappa}B signalling},
  url          = {http://dx.doi.org/10.1111/bjh.12588},
  volume       = {163},
  year         = {2013},
}

Chicago
Pede, Valerie, Ans Rombout, Jolien Vermeire, Evelien Naessens, Hanne Vanderstraeten, Jan Philippé, and Bruno Verhasselt. 2013. “Expression of ZAP70 in Chronic Lymphocytic Leukaemia Activates NF-κB Signalling.” British Journal of Haematology 163 (5): 621–630.
APA
Pede, V., Rombout, A., Vermeire, J., Naessens, E., Vanderstraeten, H., Philippé, J., & Verhasselt, B. (2013). Expression of ZAP70 in chronic lymphocytic leukaemia activates NF-κB signalling. BRITISH JOURNAL OF HAEMATOLOGY, 163(5), 621–630.
Vancouver
1.
Pede V, Rombout A, Vermeire J, Naessens E, Vanderstraeten H, Philippé J, et al. Expression of ZAP70 in chronic lymphocytic leukaemia activates NF-κB signalling. BRITISH JOURNAL OF HAEMATOLOGY. 2013;163(5):621–30.
MLA
Pede, Valerie, Ans Rombout, Jolien Vermeire, et al. “Expression of ZAP70 in Chronic Lymphocytic Leukaemia Activates NF-κB Signalling.” BRITISH JOURNAL OF HAEMATOLOGY 163.5 (2013): 621–630. Print.