Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription
Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription
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Sezary 细胞中 SATB1 表达缺陷通过调节 FasL/CD95L 转录导致细胞凋亡抵抗
DOI：
10.1182/blood-2010-07-294819
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发表时间：
2011-04-07
期刊：
影响因子：
20.3
通讯作者：
Zhou, Youwen
中科院分区：
文献类型：
--
作者：
Wang, Yang;Su, Mingwan;Zhou, Youwen
Sezary综合征（SS）是一种侵袭性皮肤T细胞淋巴瘤亚型，其特征是循环白血病Sezary细胞。这些恶性细胞的积累已被证明是对细胞凋亡，特别是活化诱导的细胞死亡的抗性的结果。然而，细胞凋亡抵抗的机制仍不清楚。通过对分离自SS患者的纯化的CD 4（+）CD 7（-）Sezary细胞和培养的Sezary细胞的基因转录谱进行表征，发现Sezary细胞缺乏特异性AT富集区结合蛋白1（SATB 1）的表达，SATB 1是T细胞发育和成熟的关键调节因子。逆转录病毒介导的基因转导显示，SATB 1恢复在培养的Sezary细胞（Hut 78）触发自发性细胞死亡和致敏Hut 78细胞活化诱导的细胞死亡，与相关的激活caspase 8和caspase 3。此外，在培养的Sezary细胞中恢复SATB 1表达后，在转录和翻译水平上增加了Sezary细胞中FasL的内源性表达。这些结果表明，SATB 1在Sezary细胞表达的缺陷起着重要的作用，在SS的发病机制，引起细胞凋亡阻力。因此，SATB 1表达的恢复可能代表了SS的潜在分子靶向治疗，目前尚不能治愈。（血。2011;117（14）：3826-3835）
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)