Expression of special AT-rich sequence-binding protein 1 is an independent prognostic factor in cutaneous T-cell lymphoma

Abstract

Cutaneous T-cell lymphoma (CTCL) is a group of slowly progressive, lymphoproliferative disorders characterized by localization of neoplastic T lymphocytes to the skin. The most common type of CTCL is mycosis fungoides which has a mild clinical course with slow and long progression. The rate of progression is generally slow and takes many years but often remains unpredictable. Special AT-rich sequence-binding protein-1 (SATB1) is a global chromatin organizer which controls gene expression by folding and remodeling chromatin, but which also regulates the level of histone methylation and acetylation, important in differentiation and apoptosis. The aim of the present study was to determine if SATB1 may be considered a prognostic and predictive factor of CTCL. The results showed that moderate and high expression of SATB1 correlate with significantly better prognosis of CTCL patients. Moreover, we showed that downregulation of SATB1 in Jurkat cells caused their resistance to activation-induced cell death. In conclusion, SATB1 expression appears to be a strong candidate as a prognostic factor confirming the inner heterogeneous features of CTCLs.

The alterations in SATB1 and nuclear F-actin expression affect apoptotic response of the MCF-7 cells to geldanamycin

“…In the present study, we observed the decrease in Annexin V-positive cells in the response to siRNA SATB1 treatment. These observations have also been confirmed by our studies on the model of Jurkat cells [48].…”

“…The results presented in this paper suggest that SATB1 may be involved together with F-actin in chromatin reorganization during cell death. Indeed, the association between nuclear F-actin and SATB1 and their involvement in chromatin remodeling during cell death was observed by us in CHO AA8 cell line [31] and in Jurkat cells [48]. Our previous observations suggest also that the expression of cofilin-1 is essential for the activation of cell death [35].…”

The interactions between SATB1 and F-actin are important for mechanisms of active cell death

“…The significance of SATB1 expression during active cell death is controversial and requires further investigations. Downregulation of SATB1 in Jurkat cells caused their resistance to induced cell death [40]. In line with these observations, Wang et al reported that deficiency in SATB1 expression in Sézary cells caused resistance to apoptosis [41].…”

SATB1 in Malignant T Cells

“…Recent observations suggested that deficient SATB1 expression has been linked to MF pathogenesis and progression (Grzanka et al, 2012(Grzanka et al, , 2015; however, this has been questioned by another study of MF patients (Jankowska-Konsur et al, 2016). Accordingly, we analyzed SATB1 protein expression in a German cohort comprising 69 skin samples (32 patches, 23 plaques, and 14 tumors) from MF patients.…”

“…Thus, deficient SATB1 expression hampers T-cell development and results in inappropriate T-cell lineages (Alvarez et al, 2000, Kakugawa et al, 2017. Two recent studies suggested that dysregulated SATB1 expression is involved in CTCL progression: (i) there is an inverse correlation between SATB1 expression and disease stage (i.e., lower expression in more advanced disease), (ii) low SATB1 was associated with an impaired prognosis (Grzanka et al, 2012(Grzanka et al, , 2015, and (iii) T cells from patients with SS have a reduced SATB1 expression when compared to healthy control individuals (Wang et al, 2011). However, the exact impact of dysregulated SATB1 expression on the course of CTCL is still controversially discussed, because it did not correlate with MF stage in all studies (Jankowska-Konsur et al, 2016).…”