title: Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70.
abstract: BACKGROUND
  Malignant T cells in primary cutaneous T-cell lymphoma (CTCL) are genetically unstable and exhibit prolonged lifespans potentially explained by dysregulation of apoptosis, yet are responsive to apoptosis-inducing therapies. The heterodimeric protein Ku70/80 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only).
  
  
  OBJECTIVE
  To investigate the expression of Ku70/80 in CD3+ T cells derived from skin and blood in patients with CTCL and normal samples, as well as benign dermatoses.
  
  
  METHODS
  Normal (n=10), CTCL (n=9) and benign dermatoses (n=13) skin samples were stained for confocal imaging of Ku70/80 and CD3 and analysed using imaging software. Circulating CD4+ T cells in normal and CTCL peripheral blood were analysed by flow cytometry and Western blot for Ku70/80 expression (n=6).
  
  
  RESULTS
  Ku70 and Ku80 were significantly diminished in T cells of CTCL lesions relative to T cells of control skin. Decreased T-cell Ku70 expression was not a feature of the benign dermatoses psoriasis and contact dermatitis, suggesting that loss of Ku70/80 in CTCL is not simply the result of cutaneous inflammation. Reduced Ku70 was also noted in circulating CD4+ T cells in patients with CTCL with peripheral blood involvement.
  
  
  CONCLUSIONS
  Deficient expression or lack of Ku70/80 may result in genomic instability and play a role in tumorigenesis, as well as account for the increased susceptibility of malignant T cells to apoptosis-inducing treatment modalities in the setting of intrinsic resistance to apoptosis.
authors.affiliation: Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ferenczi
authors.forename: J
authors.initials: J
authors.lastname: Ohtola
authors.forename: P
authors.initials: P
authors.lastname: Aubert
authors.forename: M
authors.initials: M
authors.lastname: Kessler
authors.forename: H
authors.initials: H
authors.lastname: Sugiyama
authors.forename: A K
authors.initials: AK
authors.lastname: Somani
authors.forename: A C
authors.initials: AC
authors.lastname: Gilliam
authors.forename: J Z
authors.initials: JZ
authors.lastname: Chen
authors.forename: I
authors.initials: I
authors.lastname: Yeh
authors.forename: S
authors.initials: S
authors.lastname: Matsuyama
authors.forename: T S
authors.initials: TS
authors.lastname: McCormick
authors.forename: K D
authors.initials: KD
authors.lastname: Cooper
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D000072200:Ku Autoantigen; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen
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