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学科主题: 临床医学
题名:
Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription
作者: Wang, Yang1,2; Su, Mingwan1,3; Zhou, Liang L.4; Tu, Ping2; Zhang, Xuejun5; Jiang, Xiaoyan4,6; Zhou, Youwen1,3,5
刊名: BLOOD
发表日期: 2011-04-07
DOI: 10.1182/blood-2010-07-294819
卷: 117, 期:14, 页:3826-3835
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology
研究领域[WOS]: Hematology
关键词[WOS]: PERIPHERAL T-CELLS ; LYMPHOMA-CELLS ; CUTANEOUS-LYMPHOMAS ; ABERRANT EXPRESSION ; TYROSINE KINASE ; BINDING PROTEIN ; GENE-EXPRESSION ; DEATH RECEPTOR ; UP-REGULATION ; FAS-LIGAND
英文摘要:

Sezary syndrome (SS) is an aggressive subtype of cutaneous T-cell lymphoma that is characterized by circulating leukemic Sezary cells. The accumulation of these malignant cells has been shown to be the result of the resistance to apoptosis, in particular, activation-induced cell death. However, the mechanism of apoptosis resistance remains unknown. By characterizing the gene transcription profiles of purified CD4(+)CD7(-) Sezary cells from patients with SS and cultured Sezary cells, it was found that Sezary cells are deficient in the expression of special AT-rich region binding protein 1 (SATB1), a key regulator of T-cell development and maturation. Retrovirus-mediated gene transduction revealed that SATB1 restoration in cultured Sezary cells (Hut78) triggered spontaneous cell death and sensitized Hut78 cells to activation-induced cell death, with associated activation of caspase 8 and caspase 3. Furthermore, endogenous expression of FasL in Sezary cells was increased in transcriptional and translational levels on restoration of SATB1 expression in cultured Sezary cells. These results suggest that deficiency in SATB1 expression in Sezary cells plays an important role in SS pathogenesis by causing apoptosis resistance. Thus, restoration of SATB1 expression may represent a potential molecular targeted therapy for SS, which does not have a cure at present. (Blood. 2011;117(14):3826-3835)

语种: 英语
所属项目编号: 2010-700289 ; 81072233
项目资助者: Canadian Dermatology Foundation ; Canadian Cancer Society ; Cancer Research Society ; Leukemia &amp ; Lymphoma Society of Canada ; National Nature Science Foundation of China
WOS记录号: WOS:000289265500018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68049
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Univ British Columbia, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 4E8, Canada
2.Peking Univ, Dept Dermatol & Venerol, Hosp 1, Beijing 100871, Peoples R China
3.Vancouver Coastal Hlth Res Inst, Mol Med Lab, Chieng Genom Ctr, Vancouver, BC, Canada
4.British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
5.Anhui Med Univ, Inst Dermatol, Hefei, Peoples R China
6.Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4E8, Canada

Recommended Citation:
Wang, Yang,Su, Mingwan,Zhou, Liang L.,et al. Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription[J]. BLOOD,2011,117(14):3826-3835.
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