Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetics of cutaneous T-cell lymphoma: biomarkers and therapeutic potentials.

ABSTRACT: Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of skin-homing non-Hodgkin lymphomas. There are limited options for effective treatment of patients with advanced-stage CTCL, leading to a poor survival rate. Epigenetics plays a pivotal role in regulating gene expression without altering the DNA sequence. Epigenetic alterations are involved in virtually all key cancer-associated pathways and are fundamental to the genesis of cancer. In recent years, the epigenetic hallmarks of CTCL have been gradually elucidated and their potential values in the diagnosis, prognosis, and therapeutic intervention have been clarified. In this review, we summarize the current knowledge of the best-studied epigenetic modifications in CTCL, including DNA methylation, histone modifications, microRNAs, and chromatin remodelers. These epigenetic regulators are essential in the development of CTCL and provide new insights into the clinical treatments of this refractory disease.

SUBMITTER: Lai P

PROVIDER: S-EPMC7877166 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Epigenetics of cutaneous T-cell lymphoma: biomarkers and therapeutic potentials.

Lai Pan P Wang Yang Y

Cancer biology & medicine 20210201 1

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of skin-homing non-Hodgkin lymphomas. There are limited options for effective treatment of patients with advanced-stage CTCL, leading to a poor survival rate. Epigenetics plays a pivotal role in regulating gene expression without altering the DNA sequence. Epigenetic alterations are involved in virtually all key cancer-associated pathways and are fundamental to the genesis of cancer. In recent years, the epigenetic hallmarks of CTCL ha ...[more]

PMID: 33628583

Similar Datasets

Epigenetics in the Pathogenesis and Treatment of Cutaneous T-Cell Lymphoma.

Project description:Cutaneous T-cell lymphomas (CTCLs) comprise a group of heterogeneous diseases involving malignant T cells. The pathogenesis and etiology of CTCL are still unclear, although a large number of genetic and epidemiological studies on CTCL have been conducted. Most CTCLs have an indolent course, making early diagnosis difficult. Once large-cell transformation occurs, CTCL progresses to more aggressive types, resulting in an overall survival of less than five years. Epigenetic drugs, which have shown certain curative effects, have been selected as third-line drugs in patients with relapsing and refractory CTCL. Many studies have also identified epigenetic biomarkers from tissues and peripheral blood of patients with CTCL and suggested that epigenetic changes play a role in malignant transformation and histone deacetylase inhibitor (HDACi) resistance in CTCL. Single-cell sequencing has been applied in CTCL studies, revealing heterogeneity in CTCL malignant T cells. The mechanisms of HDACi resistance have also been described, further facilitating the discovery of novel HDACi targets. Despite the heterogeneity of CTCL disease and its obscure pathogenesis, more epigenetic abnormalities have been gradually discovered recently, which not only enables us to understand CTCL disease further but also improves our understanding of the specific role of epigenetics in the pathogenesis and treatment. In this review, we discuss the recent discoveries concerning the pathological roles of epigenetics and epigenetic therapy in CTCL.

| S-EPMC8263908 | biostudies-literature

Innovative Therapeutic Approaches in Primary Cutaneous B Cell Lymphoma.

Project description:Background: Primary cutaneous B-cell lymphomas (pCBCL) include an infrequent group of non-Hodgkin lymphomas that are limited to skin sites at the time of diagnosis. They comprise roughly 20-25% of all cutaneous lymphomas and are subdivided into primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large cell B cell lymphoma, leg type (PCDLCBCL, LT). The first two show a rather indolent course while PCDLCBCL, LT carries a worse prognosis. Intravascular large cell B-cell lymphoma is the most infrequent subtype, and its therapy is not covered in this review. Topical Therapy: For solitary, single-site PCMZL and PCFCL, several topical treatment options exist. They include, but are not limited to, excision, radiotherapy, and intralesional therapies, discussed in this review. However, in selected cases, even "watchful waiting" is reasonable. Systemic Therapy: Indolent types of pCBCL rarely require systemic treatment. However, in extended cases and more importantly DLCBCL, LT, systemic treatment is the first choice. Monoclonal anti-CD20-antibody rituximab is often used as monotherapy in PCMZL and PCFCL or combined with chemotherapy in PCDLBCL, LT. Newer options are monoclonal anti-CD40 antibody dacetuzumab, anti-PD-1 and anti-PD-L1 checkpoint inhibitors, and Bruton tyrosine kinase inhibitors. Conclusion: Indolent pCBCL are treated with a risk-adapted strategy using intralesional steroids, RT, and interferon-α as first-line treatments. Relapsing cases may profit from rituximab. In aggressive PCDLCBCL, LT, rituximab with polychemotherapy is recommended. Innovative therapies include intralesional oncolytic virotherapy, systemic monoclonal antibodies, and small molecules.

| S-EPMC7426470 | biostudies-literature

Are MicroRNAs Key to Developing Biomarkers for Cutaneous T-Cell Lymphoma?

Project description:MicroRNAs are noncoding molecules that induce epigenetic modulation, and they have been involved in tumorigenesis of solid and hematologic malignancies, including cutaneous T-cell lymphoma. MicroRNAs appear to play a role in cutaneous T-cell lymphoma pathogenesis and in disease progression. We comment on recent efforts to develop microRNA classifiers that improve cutaneous T-cell lymphoma diagnosis and predict disease course.

| S-EPMC6561652 | biostudies-literature

Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies.

Project description:Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects.

| S-EPMC2901206 | biostudies-literature

Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet.

Project description:Bladder cancer (BC) is the most common neoplasia of the urothelial tract. Due to its high incidence, prevalence, recurrence and mortality, it remains an unsolved clinical and social problem. The treatment of BC is challenging and, although immunotherapies have revealed potential benefit in a percentage of patients, it remains mostly an incurable disease at its advanced state. Epigenetic alterations, including aberrant DNA methylation, altered chromatin remodeling and deregulated expression of non-coding RNAs are common events in BC and can be driver events in BC pathogenesis. Accordingly, these epigenetic alterations are now being used as potential biomarkers for these disorders and are being envisioned as potential therapeutic targets for the future management of BC. In this review, we summarize the recent findings in these emerging and exciting new aspects paving the way for future clinical treatment of this disease.

| S-EPMC6902278 | biostudies-literature

The role of epigenetics in T-cell lymphoma.

Project description:Malignant lymphomas are a group of diseases with epigenomic abnormalities fundamental to pathogenesis and pathophysiology. They are characterized by a high frequency of abnormalities related to DNA methylation regulators (DNMT3A, TET2, IDH2, etc.) and histone modifiers (EZH2, HDAC, KMT2D/MLL2, CREBBP, EP300, etc.). These epigenomic abnormalities directly amplify malignant clones. They also originate from a hematopoietic stem cell-derived cell lineage triggered by epigenomic changes. These characteristics are linked to their high affinity for epigenomic therapies. Hematology has led disease epigenetics in the areas of basic research, clinical research, and drug discovery. However, epigenomic regulation is generally recognized as a complex system, and gaps exist between basic and clinical research. To provide an overview of the status and importance of epigenomic abnormalities in malignant lymphoma, this review first summarizes the concept and essential importance of the epigenome, then outlines the current status and future outlook of epigenomic abnormalities in malignant lymphomas.

| S-EPMC9668792 | biostudies-literature

Mechanism, Consequences, and Therapeutic Targeting of Abnormal IL15 Signaling in Cutaneous T-cell Lymphoma.

Project description:Cutaneous T-cell lymphoma (CTCL) is the most common type of primary cutaneous lymphoma. Here, we report that patients with CTCL show increased IL15 in a clinical stage-dependent manner. Mechanistically, we show that ZEB1 is a transcriptional repressor of IL15 in T cells and that hypermethylation of the ZEB1 binding region within the IL15 promoter, as seen in patients with CTCL, prevents ZEB1 binding and causes increased transcription of IL15 Using a transgenic mouse model of IL15, we provide evidence that overexpression of IL15 induces a spontaneous CTCL that mimics the human neoplasm. Excessive autocrine production of IL15 in T cells inhibits an HDAC1-mediated negative autoregulatory loop, resulting in the upregulation of HDAC1 and HDAC6 and transcriptional induction of the onco-miR-21. Interruption of IL15 downstream signaling with isotype-specific HDAC inhibitors halts (HDAC1) or significantly delays (HDAC6) the progression of CTCL in vivo and provides preclinical evidence supporting a hierarchical model of oncogenic signaling in CTCL.To date, CTCL pathogenesis remains unknown, and there are no curative therapies. Our findings not only demonstrate a critical role for IL15-mediated inflammation in cutaneous T-cell lymphomagenesis, but also uncover a new oncogenic regulatory loop in CTCL involving IL15, HDAC1, HDAC6, and miR-21 that shows differential sensitivity to isotype-specific HDAC inhibitors. Cancer Discov; 6(9); 986-1005. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

| S-EPMC5388135 | biostudies-literature

Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma.

Project description:We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity. Flow cytometry (FCM) showed two distinct T-cell populations, CD4+ and CD8+ (+/- PD1), with no CD4/CD8 co-expression and no loss of panT-cell markers in either T-cell subset. FCM, accompanied by cell-sorting (CS), permitted the physical separation of four populations, as follows: CD4+/PD1-, CD4+/PD1+, CD8+/PD1- and CD8+/PD1+. TCR gene rearrangement studies on each of the four populations (by next generation sequencing, NGS) showed that the neoplastic population was of T-cytotoxic cell lineage. IHC showed the CD8+ population to be TIA-1+, but perforin- and granzyme-negative. Moreover, histiocytic markers did not render the peculiar staining pattern, which is characteristic of acral CD8+ T-cell lymphoma (PCACD8). Compared to the entities described in the 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas, we found that the indolent lymphoma described herein differed from all of them. We submit that this case represents a hitherto-undescribed type of CTCL.

| S-EPMC9953132 | biostudies-literature

Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma.

Project description:AbstractCutaneous T-cell lymphoma (CTCL) is a rare cancer of skin-homing T cells. A subgroup of patients develops large cell transformation with rapid progression to an aggressive lymphoma. Here, we investigated the transformed CTCL (tCTCL) tumor ecosystem using integrative multiomics spanning whole-exome sequencing (WES), single-cell RNA sequencing, and immune profiling in a unique cohort of 56 patients. WES of 70 skin biopsies showed high tumor mutation burden, UV signatures that are prognostic for survival, exome-based driver events, and most recurrently mutated pathways in tCTCL. Single-cell profiling of 16 tCTCL skin biopsies identified a core oncogenic program with metabolic reprogramming toward oxidative phosphorylation (OXPHOS), cellular plasticity, upregulation of MYC and E2F activities, and downregulation of MHC I suggestive of immune escape. Pharmacologic perturbation using OXPHOS and MYC inhibitors demonstrated potent antitumor activities, whereas immune profiling provided in situ evidence of intercellular communications between malignant T cells expressing macrophage migration inhibitory factor and macrophages and B cells expressing CD74.SignificanceOur study contributes a key resource to the community with the largest collection of tCTCL biopsies that are difficult to obtain. The multiomics data herein provide the first comprehensive compendium of genomic alterations in tCTCL and identify potential prognostic signatures and novel therapeutic targets for an incurable T-cell lymphoma. This article is highlighted in the In This Issue feature, p. 1171.

| S-EPMC9148441 | biostudies-literature

Genomic landscape of cutaneous T cell lymphoma.

Project description:Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes. We performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL and matched normal cells. The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NF-κB signaling, chromatin remodeling and DNA damage response. CTCL is distinctive in that somatic copy number variants (SCNVs) comprise 92% of all driver mutations (mean of 11.8 pathogenic SCNVs versus 1.0 somatic single-nucleotide variant per CTCL). These findings have implications for new therapeutics.

| S-EPMC4552614 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data