Single-Cell Heterogeneity of Cutaneous T-Cell Lymphomas Revealed Using RNA-Seq Technologies

Rassek, Karolina; Iżykowska, Katarzyna

doi:10.3390/cancers12082129

Cited by 11 publications

(11 citation statements)

References 96 publications

(138 reference statements)

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“…Genes with potentially prognostic value were identified [9,11], but results emphasize the need for personalized precision medicine [10,12]. Moreover, skin barrier dysfunction and upregulated virus entry pathways [12] may reflect increased susceptibility for skin infections already clinically observed in CTCL patients [13].…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional Heterogeneity and the Microbiome of Cutaneous T-Cell Lymphoma

Licht

Mailänder

2022

Cells

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Cutaneous T-Cell Lymphomas (CTCL) presents with substantial clinical variability and transcriptional heterogeneity. In the recent years, several studies paved the way to elucidate aetiology and pathogenesis of CTCL using sequencing methods. Several T-cell subtypes were suggested as the source of disease thereby explaining clinical and transcriptional heterogeneity of CTCL entities. Several differentially expressed pathways could explain disease progression. However, exogenous triggers in the skin microenvironment also seem to affect CTCL status. Especially Staphylococcus aureus was shown to contribute to disease progression. Only little is known about the complex microbiome patterns involved in CTCL and how microbial shifts might impact this malignancy. Nevertheless, first hints indicate that the microbiome might at least in part explain transcriptional heterogeneity and that microbial approaches could serve in diagnosis and prognosis. Shaping the microbiome could be a treatment option to maintain stable disease. Here, we review current knowledge of transcriptional heterogeneity of and microbial influences on CTCL. We discuss potential benefits of microbial applications and microbial directed therapies to aid patients with CTCL burden.

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Section: Introductionmentioning

confidence: 99%

“…These challenges underline the need for better diagnostic and prognostic tools [8]. The variable nature of CTCL comes in hand with strong transcriptome heterogeneity (inter-patient and intra-tumoural) on both the bulk [9] and the single-cell level [10].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Heterogeneity and the Microbiome of Cutaneous T-Cell Lymphoma

Licht

Mailänder

2022

Cells

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“…The presence of immune evasion-related gene alterations leading to abnormal expression of PD1, PD-L1 and PD-L2 and co-stimulatory elements such as CD28-ICOS have also impulse the investigation of anti-PD1/PD-L1 antibodies for MF and SS patient treatment 230 . In addition, the high clonal heterogeneity detected in the tumor populations, targeting the microenvironment is being considered as an alternative therapeutic opportunity in MF and other CTCL 221,231 OTHER CTCL DISTINCT FROM MF AND SS Additional clinical variants of CTCL have been recognized in the WHO classification that include the indolent primary cutaneous CD30 (+) lymphoproliferative disorders (LPD) and the more aggressive cytotoxic CTCL subtypes: extranodal natural killer T-cell lymphoma; primary cutaneous gamma-delta Tcell lymphoma; primary cutaneous CD8(+) aggressive epidermotropic lymphoma (pcAETCL) and the subcutaneous panniculitis-like T-cell lymphoma (SPTCL) 65,232 .…”

Section: Genetic and Epigenetics Insightsmentioning

confidence: 99%

Recent advances in T-cell lymphoid neoplasms

Bigas

Rodríguez‐Sevilla

Espinosa

et al. 2022

Experimental Hematology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…These effects on the pathogenesis of CTCL have been reported in many preclinical studies ( 57 ). In addition, the mechanisms of HDACi resistance in terms of the heterogeneity of advanced MF/SS have been investigated ( 58 ).…”

Section: Histone Modification In Ctclmentioning

confidence: 99%

“…The low overall response rate (approximately 30–40%) of HDACis in CTCL is probably related to HDACi resistance in malignant T cells. Cytogenetic and genomic studies have recently provided data on the molecular mechanism for apoptosis resistance in CTCL malignant T cells and data on the molecular heterogeneity of CTCL cell populations ( Figure 2 ) ( 58 ). In one study, STAT3 and RAD23B genotypes were reported to influence primary HDACi sensitivity in Sézary cells ( 64 ).…”

Section: Histone Modification In Ctclmentioning

confidence: 99%

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

Zhang

2021

Front. Oncol.

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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.

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Single-Cell Heterogeneity of Cutaneous T-Cell Lymphomas Revealed Using RNA-Seq Technologies

Cited by 11 publications

References 96 publications

Transcriptional Heterogeneity and the Microbiome of Cutaneous T-Cell Lymphoma

Transcriptional Heterogeneity and the Microbiome of Cutaneous T-Cell Lymphoma

Recent advances in T-cell lymphoid neoplasms

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

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