Abstract
Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma (CTCL) with poor prognosis, is characterized by the clinical hallmarks of circulating malignant T cells, erythroderma and lymphadenopathy. However, highly variable clinical skin manifestations and similarities with benign mimickers can lead to significant diagnostic delay and inappropriate therapy that can lead to disease progression and mortality. SS has been the focus of numerous transcriptomic-profiling studies to identify sensitive and specific diagnostic and prognostic biomarkers. Benign inflammatory disease controls (e.g., psoriasis, atopic dermatitis) have served to identify chronic inflammatory phenotypes in gene expression profiles, but provide limited insight into the lymphoproliferative and oncogenic roles of abnormal gene expression in SS. This perspective was recently clarified by a transcriptome meta-analysis comparing SS and lymphocytic-variant hypereosinophilic syndrome, a benign yet often clonal T-cell lymphoproliferation, with clinical features similar to SS. Here we review the rationale for selecting lymphocytic-variant hypereosinophilic syndrome (L-HES) as a disease control for SS, and discuss differentially expressed genes that may distinguish benign from malignant lymphoproliferative phenotypes, including additional context from prior gene expression studies to improve understanding of genes important in SS.
Highlights
Cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of skin homing T-cell malignancies, with mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) accounting for the majority of cases
We identified seven genes upregulated in lymphocytic-variant hypereosinophilic syndrome (L-HES)
The shared expression of DNM3 in SS and L-HES is surprising because DNM3 is a component of two multi-gene panels that differentiated SS from MF and benign inflammatory dermatoses (BID) cases including psoriasis, atopic dermatitis, and benign erythroderma with sensitivity and specificity over 95% [8,16]
Summary
Cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of skin homing T-cell malignancies, with mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS) accounting for the majority of cases These two variants present with highly variable clinical skin inflammation that can be mistaken for benign mimickers, such as psoriasis, atopic dermatitis and other benign inflammatory dermatoses (BID) [1,2,3]. T-cell population suitable for studies of stage progression, and the evolution of neoplastic phenotypes This role was recently filled by a benign T-cell lymphoproliferative disorder known as lymphocytic-variant hypereosinophilic syndrome (L-HES) [22], which has skin inflammation and hematologic abnormalities that resemble SS [23,24,25,26,27,28,29]. We will incorporate into perspective prior gene expression and functional studies of SS that together may distinguish characteristics of malignant and benign lymphoproliferative phenotypes, and their significance
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