title: Thalidomide regulation of NF-κB proteins limits Tregs activity in chronic lymphocytic leukemia.
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.
  
  
  OBJECTIVE
  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.
  
  
  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 glucocorticoid induced 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 + CD25 high GITR + ).
  
  
  CONCLUSIONS
  These results might indicate that thalidomide not only regulates TNF but also directly interferes with NF-κB components.
authors.affiliation: Department of Experimental Hematooncology, Medical University of Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Skórka
authors.forename: Nupur
authors.initials: N
authors.lastname: Bhattacharya
authors.forename: Paulina
authors.initials: P
authors.lastname: Własiuk
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kowal
authors.forename: Daniel
authors.initials: D
authors.lastname: Mertens
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszyńska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Giannopoulos
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000368:Aged; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013792:Thalidomide / Q000494:pharmacology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
chemical_list: D008562:Membrane Glycoproteins; D016328:NF-kappa B; D013792:Thalidomide; D051746:ZAP-70 Protein-Tyrosine Kinase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1