Malignant T cells in cutaneous T‐cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70
K Ferenczi, J Ohtola, P Aubert, M Kessler… - British Journal of …, 2010 - academic.oup.com
K Ferenczi, J Ohtola, P Aubert, M Kessler, H Sugiyama, AK Somani, AC Gilliam, JZ Chen…
British Journal of Dermatology, 2010•academic.oup.comBackground 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 …
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 …
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.
Oxford University Press