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, H. Sugiyama, Ally-Khan Somani, A. C. Gilliam, J. Z. Chen, I. Yeh, S. Matsuyama, T. S. McCormick, K. D. Cooper

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 Ku7080 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). Objectives To investigate the expression of Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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.

Original languageEnglish (US)
Pages (from-to)564-571
Number of pages8
JournalBritish Journal of Dermatology
Volume163
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

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Cutaneous T-Cell Lymphoma
T-Lymphocytes
Apoptosis
Proteins
Skin Diseases
Skin
Genomic Instability
Contact Dermatitis
Psoriasis
DNA Repair
Flow Cytometry
Carcinogenesis
Software
Western Blotting
Inflammation
Therapeutics

Keywords

  • apoptosis
  • cutaneous T-cell lymphoma
  • Ku70

ASJC Scopus subject areas

  • Dermatology

Cite this

Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70. / Ferenczi, K.; Ohtola, J.; Aubert, P.; Kessler, M.; Sugiyama, H.; Somani, Ally-Khan; Gilliam, A. C.; Chen, J. Z.; Yeh, I.; Matsuyama, S.; McCormick, T. S.; Cooper, K. D.

In: British Journal of Dermatology, Vol. 163, No. 3, 09.2010, p. 564-571.

Research output: Contribution to journalArticle

Ferenczi, K, Ohtola, J, Aubert, P, Kessler, M, Sugiyama, H, Somani, A-K, Gilliam, AC, Chen, JZ, Yeh, I, Matsuyama, S, McCormick, TS & Cooper, KD 2010, 'Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70', British Journal of Dermatology, vol. 163, no. 3, pp. 564-571. https://doi.org/10.1111/j.1365-2133.2010.09812.x
Ferenczi, K. ; Ohtola, J. ; Aubert, P. ; Kessler, M. ; Sugiyama, H. ; Somani, Ally-Khan ; Gilliam, A. C. ; Chen, J. Z. ; Yeh, I. ; Matsuyama, S. ; McCormick, T. S. ; Cooper, K. D. / Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70. In: British Journal of Dermatology. 2010 ; Vol. 163, No. 3. pp. 564-571.
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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 Ku7080 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). Objectives To investigate the expression of Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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.",
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AU - Ferenczi, K.

AU - Ohtola, J.

AU - Aubert, P.

AU - Kessler, M.

AU - Sugiyama, H.

AU - Somani, Ally-Khan

AU - Gilliam, A. C.

AU - Chen, J. Z.

AU - Yeh, I.

AU - Matsuyama, S.

AU - McCormick, T. S.

AU - Cooper, K. D.

PY - 2010/9

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N2 - 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 Ku7080 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). Objectives To investigate the expression of Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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.

AB - 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 Ku7080 is known to play a role in DNA repair (Ku70 and Ku80) and inhibition of apoptosis (Ku70 only). Objectives To investigate the expression of Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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 Ku7080 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.

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