Abstract
IL-21 and CpG ODN Are Synergistic in Their Ability To Induce Apoptosis of Chronic Lymphocytic Leukemia (CLL) Cells and Benign B1 Cells
Blood, Vol.106(11), pp.5022-5022
11/16/2005
DOI: 10.1182/blood.V106.11.5022.5022
Abstract
Abstract
We previously reported the TLR9 ligand CpG ODN can induce apoptosis of CLL cells. Interleukin 21 (IL-21), a recently discovered cytokine with structural homology to IL-2, IL-4 and IL-15, has pleiotropic effects on lymphocyte populations including NK, T and B cells. IL-21 is known to co-stimulate normal human B cell proliferation induced by CD40 ligation, and to inhibit B cell proliferation induced by anti-IgM antibodies and IL-4. We explored the impact of these two agents on CLL because of the overlapping nature of their signaling pathways. Gene chip array studies demonstrated CLL cells express the receptor for IL-21, and expression of this receptor is upregulated by CpG ODN. IL-21 as a single agent induced apoptosis of CLL cells in most samples studied. The combination of IL-21 and CpG ODN induced a greater degree of apoptosis than either agent alone.
Figure Figure
Dosing studies demonstrated synergy between these two agents in their ability to induce apoptosis of CLL cells.
Figure Figure
The effect of IL-21 and CpG ODN was also evaluated in peripheral blood from normal donors, and in umbilical cord blood. In both types of samples, therapy preferentially eliminated CD5(+) B-cells. Monoclonal antibody against CD5, but not control antibody, was able to inhibit the pro-apoptotic effect of IL-21. Our results suggest treatment with IL-21 and CpG ODN preferentially eliminates CD5(+) B cells in both malignant and benign samples, and may be a useful combination for the treatment of CLL or autoimmune disorders dependent elevated B1 cell levels. Ongoing studies are exploring the underlying signaling pathways which might be responsible for these effects.
Details
- Title: Subtitle
- IL-21 and CpG ODN Are Synergistic in Their Ability To Induce Apoptosis of Chronic Lymphocytic Leukemia (CLL) Cells and Benign B1 Cells
- Creators
- Bernd Jahrsdoerfer - University of IowaSue E. Blackwell - University of IowaJames E. Wooldridge - University of IowaMelinda W. Andreski - HoldenLaura S. Jacobus - University of IowaChristiana M. Taylor - University of IowaGeorge J. Weiner - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Blood, Vol.106(11), pp.5022-5022
- DOI
- 10.1182/blood.V106.11.5022.5022
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 11/16/2005
- Academic Unit
- Holden Comprehensive Cancer Center; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984363431002771
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