Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells

Bernd Jahrsdörfer; James E Wooldridge; Sue E Blackwell; Christiana M Taylor; Thomas S Griffith; Brian K Link; George J Weiner

doi:10.1189/jlb.0604373

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Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells

Journal article

Peer reviewed

Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells

Bernd Jahrsdörfer, James E Wooldridge, Sue E Blackwell, Christiana M Taylor, Thomas S Griffith, Brian K Link and George J Weiner

Journal of leukocyte biology, Vol.77(3), pp.378-387

03/2005

DOI: 10.1189/jlb.0604373

PMID: 15582984

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Abstract

Immunostimulatory oligodeoxynucleotides (IS ODN) can mediate a number of immunologic effects. We previously demonstrated that treatment of B cell chronic lymphocytic leukemia (B-CLL) cells with one class of IS ODN, CpG ODN, alters their phenotype and increases their immunogenicity. Here, we demonstrate that in contrast to the classic understanding of CpG ODN as inhibitors of B cell apoptosis, IS ODN including CpG ODN induce apoptosis in B-CLL cells. It is important that these changes are seen not only with CpG ODN but with ODN that lack the classical CpG motif. B-CLL cells from 20 subjects were treated in vitro with IS ODN for up to 7 days. IS ODN treatment resulted in increased numbers of apoptotic cells in 13 out of 20 B-CLL samples. IS ODN enhanced apoptosis in samples with 13q deletion as a single aberration and had a heterogeneous effect on apoptosis in samples with other aberrations including 17p deletion, 11q deletion, or trisomy 12. Induction of apoptosis did not correlate with expression of the CpG ODN receptor Toll-like receptor 9. Apoptosis was dependent on the activation of caspases and was accompanied by up-regulation of CD95/Fas and its ligand. We conclude that IS ODN including CpG ODN can induce apoptosis of most B-CLL samples. The ability of IS ODN to induce apoptosis differs based on cytogenetic status. Up-regulation of CD95/Fas may play a role in IS ODN-induced apoptosis of B-CLL.

Receptors, Tumor Necrosis Factor - metabolism

Oligodeoxyribonucleotides - immunology

Apoptosis - drug effects

Humans

Middle Aged

DNA-Binding Proteins - drug effects

Receptors, Cell Surface - metabolism

Toll-Like Receptor 9

Immunophenotyping

Male

Receptors, TNF-Related Apoptosis-Inducing Ligand

fas Receptor - metabolism

DNA-Binding Proteins - metabolism

Apoptosis - immunology

Caspases - metabolism

Receptors, Cell Surface - drug effects

Leukemia, Lymphocytic, Chronic, B-Cell - metabolism

Aged, 80 and over

Female

Ligands

Aged

Apoptosis - physiology

Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy

Oligodeoxyribonucleotides - pharmacology

Details

Title: Subtitle: Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells
Creators: Bernd Jahrsdörfer - Holden Comprehensive Cancer Center, 5970Z JPP, The University of Iowa, Iowa City, IA 52242, USA
James E Wooldridge
Sue E Blackwell
Christiana M Taylor
Thomas S Griffith
Brian K Link
George J Weiner
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.77(3), pp.378-387
DOI: 10.1189/jlb.0604373
PMID: 15582984
NLM abbreviation: J Leukoc Biol
ISSN: 0741-5400
eISSN: 1938-3673
Grant note: R01 CA 77764 / NCI NIH HHS P50 CA 97274-01 / NCI NIH HHS
Language: English
Date published: 03/2005
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984094534802771

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