Patterns of Gene Expression in Cutaneous T-Cell Lymphoma: Systematic Review of Transcriptomic Studies in Mycosis Fungoides

Abstract

Mycosis fungoides (MF) is the most prevalent type of skin lymphoma. In its early stages, it has a favorable prognosis. However, in its late stages, it is associated with an increased risk of mortality. This systematic review aimed to identify the transcriptomic changes involved in MF pathogenesis and progression. A literature search was conducted using the database PubMed, followed by the extraction of 2245 genes which were further filtered to 150 recurrent genes that appeared in two or more publications. Categorization of these genes identified activated pathways involved in pathways such as cell cycle and proliferation, chromosomal instability, and DNA repair. We identified 15 genes implicated in MF progression, which were involved in cell proliferation, immune checkpoints, resistance to apoptosis, and immune response. In highlighting the discrepancies in the way MF transcriptomic data is obtained, further research can focus on not only unifying their approach but also focus on the 150 pertinent genes identified in this review.

TOX Expression in Mycosis Fungoides and Sezary Syndrome

“…Genetic aberration along with cytokinc and inflammatory cell changes have been proposed as a putative candidate [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ] sometimes providing contradictory results due to the small sample size or the use of different technique of investigation (immunohistochemistry and/or molecular biology analysis). Genetic aberration involving cell cycle and proliferation, chromosomal instability, and DNA repair have been observed in MF/SS [ 28 ]. Those genes are involved in different pathways such as epigenetic and/or chromatin regulation, TCR and T-cell/ cytokine signalling, Jak/signal transducer and activator of transcription (STAT), and phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt) and NF-kB pathway, configuring that a complex mutational landascape may be related to MF/SS pathogenesis [ 27 , 29 , 30 ].…”

Real-Life Barriers to Diagnosis of Early Mycosis Fungoides: An International Expert Panel Discussion

“…Evaluation of biopsy specimens has also identified genes related to disease progression, including cell proliferation, immune checkpoints, resistance to apoptosis, and immune response, that are upregulated in late-versus early-stage MF, and thus potentially prognostic [57,58]. Liquid biopsy sampling also revealed an association between high plasma levels of exosomal miRNA-1246, cell-free miRNA-155, and cell-free miRNA-1246 with advanced MF lesions, which may serve as promising non-invasive biomarkers [59].…”

Diagnosis of Early Mycosis Fungoides

“…In such cases, the detection of some molecules including TOX and CADM1, clonality analysis by NGS, and examination of miR expression might contribute to the diagnosis. There has been gradual increase in transcriptomic studies of MF [ 55 ]. Although skin samples of MF used in transcriptomic studies include many non-tumor cells, the exploration of the genome-wide expression of individual genes in skin samples may be useful in elucidating the pathogenesis and improving the diagnosis of MF.…”