Project description:Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. To characterize the tumor microenvironment at single-cell spatial resolution, we applied NanoString CosMx Spatial Molecular Imaging (SMI) with a 1000-plex panel to formalin-fixed paraffin-embedded (FFPE) skin biopsies from MF patients. This dataset includes patch-stage and plaque-stage MF lesions from 16 patients, comprising 65,717 cells profiled across multiple fields of view per patient.
Project description:FOXM1 is a vital transcription factor associated with proliferation, expressed extensively and dynamically throughout the cell cycle. Its overexpression in mycosis fungoides correlates with a poor prognosis. However, the specific role of FOXM1 in the pathogenesis of mycosis fungoides remains unclear. In this study, we silenced FOXM1 in the MyLa cell line, which is representative of mycosis fungoides, by transducing it with a lentivirus vector containing shRNA targeting the FOXM1 gene. By comparing MyLa cells transduced with scrambled shRNA as the control, we observed distinct gene expression profiles, notably a decrease in the expression of cell cycle-related genes and an increase in apoptosis-related genes. These changes align with the phenotypic alterations of MyLa cells following FOXM1 silencing.
Project description:Mycosis fungoides patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present EORTC multicenter study, the genomic profile of 41 skin biopsies from tumor-stage mycosis fungoides was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2 and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21 and 10q26qter were defined as prognostic markers exhibiting a significant correlation with overall survival (P= .042, P= .017 and P= .022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (> 5 DNA aberrations), showing that the genomic unstable group had a shorter overall survival (P=.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B and MTAP), and 10q26qter (MGMT and EBF3) may play an important role in prognosis. In addition, we describe the MFt genomic instability profile.
Project description:We used targeted single cell RNA sequencing using a gene set composed of the BD Rhapsody Human Immune Response Panel, TCR panel, and a custom panel of 61 malignancy-associated genes and T/B cell receptor sequencing to characterize single cell populations in hypopigmented mycosis fungoides (HMF). Using a reference mapping model built on publically deposited classic mycosis fungoides single cell RNA sequencing datasets, we identified a predicted malignant cell population independent from the clonal T cell population in HMF.
