title: Deficiency of SATB1 expression in Sezary cells causes apoptosis resistance by regulating FasL/CD95L transcription.
abstract: Sézary syndrome (SS) is an aggressive subtype of cutaneous T-cell lymphoma that is characterized by circulating leukemic Sézary 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(-) Sézary cells from patients with SS and cultured Sézary cells, it was found that Sézary 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 Sézary 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 Sézary cells was increased in transcriptional and translational levels on restoration of SATB1 expression in cultured Sézary cells. These results suggest that deficiency in SATB1 expression in Sézary 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.
authors.affiliation: Department of Dermatology and Venerology, Peking University First Hospital, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Mingwan
authors.initials: M
authors.lastname: Su
authors.forename: Liang L
authors.initials: LL
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Tu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jiang
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D001773:Blood Cells / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D012751:Sezary Syndrome / Q000235:genetics / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D036961:Matrix Attachment Region Binding Proteins; C076189:SATB1 protein, human