Insights Into the Molecular and Cellular Underpinnings of Cutaneous T Cell Lymphoma.

Insights Into the Molecular and Cellular Underpinnings of Cutaneous T Cell Lymphoma. Yale J Biol Med. 2020 Mar;93(1):111-121 Authors: Yumeen S, Girardi M Abstract Cutaneous T cell lymphoma (CTCL) is a rare malignancy of skin-homing T lymphocytes. Advances in whole exome sequencing have identified a vast number of both single nucleotide variants (SNVs) and genomic copy number alterations (GCNAs) as driver mutations present in CTCL cells. These alterations cluster within several key pathways - T cell/NF-κB/JAK-STAT activation, cell cycle dysregulation/apoptosis, and DNA structural dysregulation affecting gene expression - allowing the maintenance of a population of proliferating, activated malignant T lymphocytes. While much of the clinical spectrum, genetic alterations, and oncogenic behavior of CTCL have been elucidated, little is known about the etiology that underlies CTCL malignant transformation and progression. Herein, we review the epidemiology, clinical presentation, and pathophysiology of CTCL to provide a perspective on CTCL pathogenesis. We outline a series of alterations by which mature, activated T lymphocytes are endowed with apoptosis resistance and cutaneous persistence. Subsequent genomic alterations including the loss of chromosomal structural controls further promote proliferation and constitutive T cell activation. CTCL cells are both malignant cells and highly functional T cells that can have major cutaneous and ...
Source: The Yale Journal of Biology and Medicine - Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research