Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2014, vol. 23, nr 1, January-February, p. 25–32

Publication type: original article

Language: English

Thalidomide Regulation of NF-κB Proteins Limits Tregs Activity in Chronic Lymphocytic Leukemia

Katarzyna Skórka1,C,D,F, Nupur Bhattacharya2,B,F, Paulina Własiuk1,B,F, Małgorzata Kowal3,A,B,F, Daniel Mertens2,4,A,B,E,F, Anna Dmoszyńska3,E,F, Krzysztof Giannopoulos1,3,A,B,C,E,F

1 Department of Experimental Hematooncology, Medical University of Lublin, Poland

2 Department of Internal Medicine III, University of Ulm, Germany

3 Department of Hematooncology and BMT Unit, Medical University of Lublin, Poland

4 “Mechanisms of Leukemogenesis” Cooperation Unit, German Cancer Research Center DKFZ, Heidelberg, Germany

Abstract

Background. Thalidomide may represent a novel therapeutic strategy in the treatment of chronic lymphocytic leukemia (CLL). Since the activation of nuclear factor kappa B (NF-κB) causes not only malignant transformation and tumor progression, but also allows tumor cells to evade immune surveillance, NF-κB signaling components might constitute a potential target for future therapy in CLL.
Objectives. The current study is an attempt to characterize proteins regulated by thalidomide. Thalidomide’s influence on NF-κB proteins and on regulatory T cells (Treg) in CLL was investigated.
Material and Methods. A total of 15 patients with CLL were treated with a combined thalidomide/fludarabine regimen. Peripheral blood mononuclear cells were separated by Ficoll density gradient centrifugation. To evaluate glucocorticoidinduced tumour-necrosis-factor-receptor-related protein (GITR) expression in regulatory T cells, cells incubated with anti-CD3, ani-CD4 and anti-CD25 were permeabilized and then stained with anti-FOXP3 and analyzed using flow cytometry. Human TNF enzyme-linked immunosorbent assay (ELISA) was used to determine the tumor necrosis factor (TNF) levels in the serum. To evaluate NF-κB activity, chemiluminescent oligonucleotide-based ELISA was performed.
Results. It was found that thalidomide regulates NF-κB activity differentially, and the activity of certain NF-κB components correlated with TNF levels and T regulatory cell (CD4+CD25highGITR+).
Conclusion. These results might indicate that thalidomide not only regulates TNF but also directly interferes with NF-κB components.

Key words

nucelar factor kappa B (NF-κB), thalidomide, chronic lymphocytic leukemia (CLL), regulatory T cells (Treg), tumor necrosis factor (TNF).

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