Project description:Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.
Project description:CTCLs are a group of non-Hodgkin lymphomas, with non-aggressive forms (Mycosis fungoides (MF)) initially presenting with features of cutaneous eczema or psoriasis, posing a challenge for clinical and histological diagnosis. Using spatial transcriptomics, we hope to delineate the molecular signatures of CTCL to provide novel avenues for diagnostics and therapies.
Project description:CTCLs are a group of non-Hodgkin lymphomas, with non-aggressive forms (Mycosis fungoides (MF)) initially presenting with features of cutaneous eczema or psoriasis, posing a challenge for clinical and histological diagnosis. Using scRNA-seq, we hope to delineate the molecular signatures of CTCL to provide novel avenues for diagnostics and therapies.
Project description:FFPE skin biopsy samples from patients with CTCL, dermatitis, or healthy controls were profiled by NanoString gene expression analysis A classifier was constructed that was able to identify mycosis fungoides (MF) samples from dermatitis and healthy controls.
Project description:miR-155 is a microRNA associated with poor prognosis in lymphoma and leukemia and has been implicated in the progression of Mycosis Fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). In this study, we developed and tested Cobomarsen (MRG-106), a locked nucleic acid-modified oligonucleotide inhibitor of miR-155. In MF cell lines in vitro, inhibition of miR-155 with Cobomarsen de-repressed direct miR-155 targets, decreased expression of multiple gene pathways associated with cell survival, reduced survival signaling, decreased cell proliferation, and activated apoptosis. We identified a set of genes that are significantly regulated by Cobomarsen, which includes direct and downstream targets of miR-155.
Project description:We performed transcriptome analysis and multimodal data integration of the transcriptome and the microbiome of the skin of Mycosis fungoides Patients.
Project description:SATB1 is an important T-cell specific chromatin organizer in cutaneous T cell lymphoma, while its expression and function in Mycosis fungoides (MF) remain ambiguous. RNA-sequencing was conducted to investigate the genes regulated by SATB1 in MF-derived MJ cells by RNA-sequencing after SATB1-knockdown. With the criteria of P<0.05 and |fold change|>1.3, there were 988 genes upregulated and 1373 genes downregulated in SATB1-silencing MJ cells and further subjected to KEGG analysis. SATB1 silencing in MJ cells showed that SATB1 upregulated genes involved in eosinophil recruitment, including STAT3 and IL13, and downregulated genes in cell cycle progression.
Project description:We studied gene expression profiles of 17 cutaneous B-cell lymphomas that were collected with 4-6 millimeter skin punch biopsies. We also included tissue from 2 cases of mycosis fungoides (MF), 3 normal skin biopsies and 3 tonsils to create a framework for further interpretation. A hierarchical cluster algorithm was applied for data analysis. Our results indicate that small amounts of skin tissue can be used successfully to perform microarray analysis and result in distinct gene expression patterns. Duplicate specimens clustered together demonstrating a reproducible technique. Within the cutaneous B-cell lymphoma specimens two specific B-cell differentiation stage signatures of germinal center B-cells and plasma cells could be identified. Primary cutaneous follicular and primary cutaneous diffuse large B-cell lymphomas had a germinal center B-cell signature while a subset of marginal zone lymphomas demonstrated a plasma cell signature. Primary and secondary follicular B-cell lymphoma of the skin were closely related, despite previously reported genetic and phenotypic differences. In contrast primary and secondary cutaneous diffuse large B-cell lymphoma were less related to each other. This pilot study allows a first glance into the complex and unique microenvironment of B-cell lymphomas of the skin and provides a basis for future studies, that may lead to the identification of potential histologic and prognostic markers as well as therapeutic targets.