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Malignant T cells in cutaneous T‐cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70
Author(s) -
Ferenczi K.,
Ohtola J.,
Aubert P.,
Kessler M.,
Sugiyama H.,
Somani A.K.,
Gilliam A.C.,
Chen J.Z.,
Yeh I.,
Matsuyama S.,
McCormick T.S.,
Cooper K.D.
Publication year - 2010
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2010.09812.x
Subject(s) - ku70 , cutaneous t cell lymphoma , apoptosis , flow cytometry , medicine , ku80 , cancer research , lymphoma , carcinogenesis , immunology , pathology , dna repair , biology , mycosis fungoides , cancer , dna , biochemistry , genetics , dna binding protein , gene , transcription factor
Summary 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). Objectives 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.