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Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70.

ABSTRACT: 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).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.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).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.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.

SUBMITTER: Ferenczi K

PROVIDER: S-EPMC3145455 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70.

Ferenczi K K 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

The British journal of dermatology 20100901 3

<h4>Background</h4>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).<h4>Objectives</h4>To investigate the expression of Ku70/80 in CD3+ T cells derived from skin and blood in patients with CTCL and ...[more]

PMID: 20408834

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Project description:AimRecent studies suggested a role for IL31 in the pathogenesis of pruritus and disease severity in patients with cutaneous T cell lymphomas (CTCL). However, discrepant results were reported for IL31 serum levels, transcriptional expression levels or immunohistochemistry studies and its relation to pruritus intensity and/or disease severity in CTCL. Most studies did not distinguish between different CTCL variants. We investigated IL31 serum levels in different subtypes of CTCL, including Mycosis Fungoides (MF) (typically not pruritic), Folliculotropic Mycosis Fungoides (FMF) and Sézary syndrome (SS) (both often pruritic).MethodsFrom 54 CTCL patients (17 SS, 21 FMF and 16 classic MF) serum samples were analyzed with a high sensitivity V-PLEX immunoassay for IL31. The study group included 35/54 (65%) patients with complaints of pruritus. Thirty-five patients had advanced stage disease (≥stage IIB). A visual analog scale score (VAS score) for pruritus was available in 29 CTCL patients (7 SS, 9 FMF and 13 classic MF) and in other cases complaints of pruritus were retrieved from medical records. qPCR analyses for IL31 expression were performed in lesional skin biopsies from 8 CTCL patients. Serum samples from 4 healthy individuals without pruritus and from 5 atopic dermatitis (AD) patients with severe pruritus were included as controls.ResultsIn 11/54 (20%) of CTCL patients low serum levels of IL31 were detected (mean 0.48 pg/mL, range 0.20-1.39 pg/mL) including 6/17 (35%) SS patients (mean 0.57 pg/mL) and 5/21 (24%) FMF patients (mean 0.33 pg/mL). All 11 patients with detectable levels of IL31 reported complaints of moderate to severe pruritus and 9/11 patients presented with advanced stage disease (≥IIB). qPCR analyses resulted in lowly expressed IL31 expression levels in 4 of 8 patients; these patients all suffered from pruritus and advanced stage disease.ConclusionsTranslational and transcriptional expression levels of IL31 were very low or undetectable in CTCL patients. Detectable low IL31 serum levels were exclusively observed in SS and FMF patients and not in patients with classic MF. However, these marginal IL31 levels in a small proportion of CTCL patients do not support an essential role for IL31 in CTCL patients.

Dataset Information

Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70.

Publications

Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70.

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