Gene expression studies of cutaneous T-cell lymphoma (CTCL) span a decade, yet pathogenesis is poorly understood and diagnosis remains a challenge. This review examines the varied approaches to gene expression analysis of CTCL, with emphasis on cell populations, control selection, and expression data collection. Despite discordant results, several dysregulated genes have been identified across multiple studies including PLS3, KIR3DL2, TWIST1, and STAT4. Here, we provide an overview of the most consistently expressed genes across different studies and bring them together through common pathways biologically relevant to CTCL. Four pathways, evasion of activation-induced cell death, T-helper 2 lymphocyte differentiation, TGF-β receptor expression, and TNF receptor ligands, appear to encompass the most frequently affected genes, hypothetically providing insight to the disease pathogenesis.
The practice of pre-emptive individualized medicine is predicated on the discovery, development and application of biomarkers in specific clinical settings. Mycosis fungoides and Sézary syndrome are the two most common type of cutaneous T-cell lymphoma, yet diagnosis, prognosis and disease monitoring remain a challenge. In this review, we discuss the current state of biomarker discovery in mycosis fungoides and Sézary syndrome, highlighting the most promising molecules in different compartments. Further, we emphasize the need for continued multicentre efforts to validate available and new biomarkers and to develop prospective combinatorial panels of already discovered molecules.
Studies have examined gene expression changes in Sézary syndrome (SS), but disease pathogenesis remains largely unknown, and diagnosis and treatment are difficult.
TOX
is a transcription factor involved in CD4+ T-cell development with downstream effects on
RUNX3
, a known tumor suppressor gene. We sought to identify genes involved in SS disease pathogenesis with the potential to enable diagnosis and treatment. We utilized previously reported transcriptome sequencing data to construct a list of candidate genes, which was narrowed using pathway analysis. qRT-PCR confirmed
TOX
upregulation (>7 fold increase) in SS (
n
= 5), as well as two established markers,
PLS3
and
KIRD3DL2.
We also evaluated expression of members of the TOX-RUNX3 pathway and confirmed downregulation of
RUNX3
(0.59 fold decrease) and upregulation of
GATA3
(2 fold increase). Moreover,
TOX
and
RUNX3
expression were significantly inversely proportional. Using siRNA to suppress TOX, we demonstrated that TOX knockdown rescues RUNX3 expression and reduces cell viability. We evaluated TOX protein expression in paraffin-embedded skin biopsies with immunohistochemistry, showing nuclear staining of CTCL infiltrates, suggesting it is a candidate diagnostic biomarker. Further studies validating our findings and evaluating the TOX-RUNX3 pathway and the role of
TOX
as a disease marker and therapeutic target are warranted.
There is considerable variation in surgical treatment patterns by both sociodemographic, treatment, and tumor characteristics. Despite low utilization, patients receiving MMS are more likely to achieve negative surgical margins and less likely to receive radiotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.