Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN

Détails

ID Serval
serval:BIB_C46F18301B4A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Modulation of malignant B cell activation and apoptosis by bcl-2 antisense ODN and immunostimulatory CpG ODN
Périodique
J Leukoc Biol
Auteur(s)
Jahrsdorfer B., Jox R., Muhlenhoff L., Tschoep K., Krug A., Rothenfusser S., Meinhardt G., Emmerich B., Endres S., Hartmann G.
ISSN
0741-5400 (Print)
ISSN-L
0741-5400
Statut éditorial
Publié
Date de publication
07/2002
Volume
72
Numéro
1
Pages
83-92
Langue
anglais
Notes
Jahrsdorfer, B
Jox, R
Muhlenhoff, L
Tschoep, K
Krug, A
Rothenfusser, S
Meinhardt, G
Emmerich, B
Endres, S
Hartmann, G
eng
Research Support, Non-U.S. Gov't
2002/07/09 10:00
J Leukoc Biol. 2002 Jul;72(1):83-92.
Résumé
Inhibition of bcl-2 expression by antisense oligodeoxynucleotides (ODN) might render bcl-2 overexpressing malignant B cells more susceptible to chemotherapy. ODN containing unmethylated CG dinucleotides (CpG) are known to activate B cells. We studied the effects of two bcl-2 antisense ODN, with (G3139) or without CG dinucleotides (NOV 2009) within the sequence, and the effects of a nonantisense, CpG-containing ODN (ODN 2006) on activation and apoptosis of malignant B cell lines and primary B-CLL cells. Without cationic lipids, no antisense-mediated inhibition of bcl-2 synthesis was achieved with G3139 and NOV 2009. Instead, G3139, but not NOV 2009, induced similar changes as ODN 2006 in proliferation, expression of costimulatory and antigen-presenting molecules, as well as in bcl-2 and bcl-xL levels of primary B-CLL cells. G3139 and ODN 2006 inhibited in vitro, spontaneous apoptosis in B-CLL cells of patients with high serum thymidine kinase activity (s-TK, marker for proliferative activity of malignant B cells), whereas in patients with low s-TK activity, apoptosis was induced. In conclusion, our results suggest that modulation of malignant B cell apoptosis by G3139 depends on its immunostimulatory properties rather than on antisense-mediated reduction of bcl-2 expression. Immunostimulatory CpG ODN may have a therapeutic potential in patients with B-CLL, especially those with low s-TK activity.
Mots-clé
Adjuvants, Immunologic/chemistry/*pharmacology, Apoptosis, Gene Expression Regulation, Humans, Leukemia, Lymphocytic, Chronic, B-Cell/genetics/*metabolism/pathology, Lymphocyte Activation, Oligodeoxyribonucleotides/chemistry/*pharmacology, Oligodeoxyribonucleotides, Antisense/*pharmacology, Phosphatidylethanolamines, Proto-Oncogene Proteins c-bcl-2/biosynthesis/*genetics, Thymidine Kinase/metabolism, Tumor Cells, Cultured, bcl-X Protein
Pubmed
Création de la notice
14/07/2017 10:09
Dernière modification de la notice
03/03/2018 21:13
Données d'usage