Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70.
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.
Ferenczi
K
K
Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA.
Ohtola
J
J
Aubert
P
P
Kessler
M
M
Sugiyama
H
H
Somani
A K
AK
Gilliam
A C
AC
Chen
J Z
JZ
Yeh
I
I
Matsuyama
S
S
McCormick
T S
TS
Cooper
K D
KD
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*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen
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