Regulation of T-Plastin Expression by Promoter Hypomethylation in Primary Cutaneous T-Cell Lymphoma

Jones, Christine L.; Ferreira, Sandra Reis; McKenzie, Robert C.; Tosi, Isabella; Caesar, Jacqueline A.; Bagot, Martine; Whittaker, Sean; Mitchell, Tracey

doi:10.1038/jid.2012.106

Cited by 31 publications

(21 citation statements)

References 33 publications

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“…Circulating Sézary cells have also been found to express the CD158k molecule, which belongs to the family of killer cell immunoglobulin‐like receptors normally expressed on a minor population of circulating NK and CD8 + T lymphocytes . T‐plastin is an actin‐binding protein normally expressed in epithelial cells but absent in cells of hematopoietic origin; the expression of PLS3 mRNA has been shown to be of potential interest in the monitoring of SS response to treatment . CTCL cells from patients with SS show significantly increased PD‐1 expression compared with those from patients with MF and healthy volunteers .…”

Section: Review Of Parameters Relevant To Prognosis In Mycosis Fungoimentioning

confidence: 99%

Prognostic factors, prognostic indices and staging in mycosis fungoides and Sézary syndrome: where are we now?

Kim²,

et al. 2014

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Mycosis fungoides is the most prevalent form of primary cutaneous T-cell lymphoma. Patients frequently present with early-stage disease typically associated with a favourable prognosis and survival of 10-35 years, but over 25% may progress to advanced disease with a median survival < 4 years, and just 13 months in those with nodal involvement. Sézary syndrome presents in advanced disease with erythroderma, blood involvement and lymphadenopathy. The Bunn and Lamberg staging system (1979) includes stages IA-IIA (early-stage disease) and IIB-IVB (advanced-stage disease) and provides prognostic information, but some patients with tumour-stage disease (IIB) have a worse prognosis than those with erythrodermic-stage (III). Conversely, patients with plaque-stage (IB) folliculotropic mycosis fungoides may have a worse outcome than those with tumour-stage (IIB). The more recent staging system of the European Organisation for the Research and Treatment of Cancer/International Society for Cutaneous Lymphoma has been designed to reflect tumour burden at different sites. However, this staging system has not been validated prospectively for prognosis. Furthermore, this staging system does not include a detailed measurement of skin tumour burden, as indicated by the modified skin weighted severity assessment tool. This assessment measures body surface area of disease and is weighted to record patch, plaque and tumour to produce a numerical value from 0·5 to 400 and is an established endpoint for clinical studies. Nor does this staging include clinicopathological features associated with a poor prognosis such as folliculotropism. Here we review the clinical, haematological, pathological and genotypic parameters outside the staging system, which may affect survival in mycosis fungoides and Sézary syndrome. Most studies are retrospective and single centre. The identification of poor prognostic factors may be used to develop a prognostic index to use alongside staging, which may be of benefit in mycosis fungoides/Sézary syndrome to identify patients with a potentially poor prognosis.

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Section: Review Of Parameters Relevant To Prognosis In Mycosis Fungoimentioning

confidence: 99%

Prognostic factors, prognostic indices and staging in mycosis fungoides and Sézary syndrome: where are we now?

Kim²,

et al. 2014

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“…Furthermore, heterogeneity of expression of PLS3 was observed within the same malignant population isolated from the same patient. 20 As there is no single suitable marker for isolation of a pure population of CTCL tumour cells, different studies have utilized different approaches. Each approach has its merits for answering certain questions but not others.…”

Section: Gene Expression Studies In Mycosis Fungoides and S Ezary Synmentioning

confidence: 99%

“…Overexpressed in SS PBMCs 6,9,21,37 and SS CD4+ T cells 6,16,17,60,61 Actin-building protein not normally expressed in T cells, 41 promoter is demethylated, 20,41 known role in actin structure elongation, 62 associated with SS cell survival and migration 37…”

Section: Pls3mentioning

confidence: 99%

Lessons learned from gene expression profiling of cutaneous T-cell lymphoma

Dulmage

Geskin

2013

Br J Dermatol

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Gene expression studies of cutaneous T-cell lymphoma (CTCL) span a decade, yet pathogenesis is poorly understood and diagnosis remains a challenge. This review examines the varied approaches to gene expression analysis of CTCL, with emphasis on cell populations, control selection, and expression data collection. Despite discordant results, several dysregulated genes have been identified across multiple studies including PLS3, KIR3DL2, TWIST1, and STAT4. Here, we provide an overview of the most consistently expressed genes across different studies and bring them together through common pathways biologically relevant to CTCL. Four pathways, evasion of activation-induced cell death, T-helper 2 lymphocyte differentiation, TGF-β receptor expression, and TNF receptor ligands, appear to encompass the most frequently affected genes, hypothetically providing insight to the disease pathogenesis.

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“…Interestingly, these genes all have large CpG islands and loss of methylation may be a mechanism for activation of these genes. Further supporting this notion, hypomethylation of CpG islands was identified in CTCL patients [23]. Ferrara et al [24] evaluated methylation patterns in 41 mycosis fungoides patients with Stage 1 disease, looking for patterns linked to increased risk of progressive disease over 12 years of follow up-observation.…”

Section: Key Pointsmentioning

confidence: 85%

Recent advances in primary cutaneous T-cell lymphoma

DeSimone

Sodha

Ignatova

et al. 2015

Current Opinion in Oncology

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PURPOSE OF REVIEW Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. RECENT FINDINGS In the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SUMMARY This is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year. Purpose of review Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. Recent findingsIn the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SummaryThis is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year.

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Regulation of T-Plastin Expression by Promoter Hypomethylation in Primary Cutaneous T-Cell Lymphoma

Cited by 31 publications

References 33 publications

Prognostic factors, prognostic indices and staging in mycosis fungoides and Sézary syndrome: where are we now?

Prognostic factors, prognostic indices and staging in mycosis fungoides and Sézary syndrome: where are we now?

Lessons learned from gene expression profiling of cutaneous T-cell lymphoma

Recent advances in primary cutaneous T-cell lymphoma

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