Structural alterations of the FAS gene in cutaneous T-cell lymphoma (CTCL).

FAS (TNF receptor superfamily member 6, also known as CD95) plays a major role in T-cell apoptosis and is often dysregulated in CTCL. We searched for structural alterations of the FAS gene with the potential to affect its function. Although several heterozygous FAS promoter single nucleotide polymorphisms (SNPs) were detected, the only homozygous one was the -671 GG SNP present in 24/80 CTCL cases (30%).

Low FAS/CD95 expression by CTCL correlates with reduced sensitivity to apoptosis that can be restored by FAS upregulation.

FAS expression was generally low in 30 of 31 cutaneous T-cell lymphoma (CTCL) cases (mycosis fungoides/Sezary syndrome, SS) as well as in 5 of 6 large plaque parapsoriasis cases (a CTCL precursor). To investigate this phenomenon, we explored FAS transcript levels, cell-surface FAS protein expression and susceptibility to FAS-mediated apoptosis in four CTCL lines (MyLa, HH, SZ4, and SeAx), freshly isolated leukemic cells from a patient with SS, an acute lymphoblastic leukemia T-cell line (Jurkat), and JFL (a FAS-low variant of Jurkat). Results confirmed low FAS expression by the leukemic SS cells, HH, SZ4, SeAx, and JFL relative to normal peripheral blood mononuclear leukocytes and the other cell lines.