Expression of CD31 in Mycosis Fungoides

Jankowska‐Konsur, Alina; Kobierzycki, Christopher; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Gomułkiewicz, Agnieszka; Glatzel-Plucińska, Natalia; Olbromski, Mateusz; Podhorska-Okołów, Marzena; Szepietowski, Jacek C.; Dzięgiel, Piotr

doi:10.21873/anticanres.11006

Cited by 22 publications

(26 citation statements)

References 21 publications

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“…Deficient SATB1 expression hampers T-cell development and results in misregulation of T-cell lineages [30,31]. Previous studies suggested that dysregulated SATB1 expression is involved in CTCL progression: low SATB1 was associated with an impaired prognosis, although SATB1 expression did not correlate with MF stages in all studies [32]. Recent data provided mechanistic evidence that the proto-oncogenic JAK3-STAT5 pathway promotes an aberrant expression of IL-5 and IL-9 through miR-155-mediated repression of SATB1 [33].…”

Section: Discussionmentioning

confidence: 87%

Synergistic cytotoxic activity of cannabinoids fromcannabis sativaagainst cutaneous T-cell lymphoma (CTCL)in-vitroandex-vivo

et al. 2020

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Cannabis sativa produces hundreds of phytocannabinoids and terpenes. Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by patches, plaques and tumors. Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood. This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells. Ethanol extracts of C. sativa were analyzed by high-performance liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Cytotoxic activity was determined using the XTT assay on My-La and HuT-78 cell lines as well as peripheral blood lymphocytes from Sézary patients (SPBL). Annexin V assay and fluorescence-activated cell sorting (FACS) were used to determine apoptosis and cell cycle. RNA sequencing and quantitative PCR were used to determine gene expression. Active cannabis compounds presenting high cytotoxic activity on My-La and HuT-78 cell lines were identified in crude extract fractions designated S4 and S5, and their synergistic mixture was specified. This mixture induced cell cycle arrest and cell apoptosis; a relatively selective apoptosis was also recorded on the malignant CD4 + CD26-SPBL cells. Significant cytotoxic activity of the corresponding mixture of pure phytocannabinoids further verified genuine interaction between S4 and S5. The gene expression profile was distinct in My-La and HuT-78 cells treated with the S4 and S5 synergistic mixture. We suggest that specifying formulations of synergistic active cannabis compounds and unraveling their modes of action may lead to new cannabis-based therapies.

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Section: Discussionmentioning

confidence: 87%

Synergistic cytotoxic activity of cannabinoids fromcannabis sativaagainst cutaneous T-cell lymphoma (CTCL)in-vitroandex-vivo

et al. 2020

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“…SATB1 plays a key role in normal T-cell development (Alvarez et al, 2000), and deregulated SATB1 expression has been implicated in CTCL pathogenesis and progression (Grzanka et al, 2012(Grzanka et al, , 2015. However, other studies questioned this notion (Jankowska-Konsur et al, 2016). Here, we report that a loss of SATB1 expression correlated with advanced disease; that is, SATB1 expression was significantly decreasing as the disease progressed from patch-over-plaque to tumor-stage were analyzed for IL-5, IL-6, IL-9, and IL-32 on quantitative PCR with GAPDH as control and ELISA.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Stage-dependent Satb1 Expressionmentioning

confidence: 99%

“…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). SATB1 expression was increased in lesions of anaplastic large-cell lymphoma, that is, a less aggressive subtype of CTCL (Wang et al, 2014).…”

Section: Introductionmentioning

confidence: 98%

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SATB1 in Malignant T Cells

Fredholm

Willerslev-Olsen

Met

et al. 2018

Journal of Investigative Dermatology

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Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.

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“…The diagnosis was established and re-evaluated based on clinical, histopathological and IHC examinations, according to the World Health Organization (WHO) classification (2008) (1). The staging was assessed according to TNMB (Tumour, Nodes, Metastases, Blood) system (ISCL/EORTC revision) presented in our previous study (24). To examine potential differences between benign and malignant skin conditions chronic benign dermatitis paraffin samples (16 lichen planus, 3 disseminated eczema cases) were used as a control.…”

Section: Specimensmentioning

confidence: 99%

Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides

Jankowska‐Konsur

Kobierzycki²,

Grzegrzółka³

et al. 2017

Acta Derm Venerol

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The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

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Expression of CD31 in Mycosis Fungoides

Cited by 22 publications

References 21 publications

Synergistic cytotoxic activity of cannabinoids fromcannabis sativaagainst cutaneous T-cell lymphoma (CTCL)in-vitroandex-vivo

Synergistic cytotoxic activity of cannabinoids fromcannabis sativaagainst cutaneous T-cell lymphoma (CTCL)in-vitroandex-vivo

SATB1 in Malignant T Cells

Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides

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