TY - JOUR
T1 - Low FAS/CD95 expression by CTCL correlates with reduced sensitivity to apoptosis that can be restored by FAS upregulation
AU - Wu, Jianqiang
AU - Nihal, Minakshi
AU - Siddiqui, Jawed
AU - Vonderheid, Eric C.
AU - Wood, Gary S.
PY - 2009/5
Y1 - 2009/5
N2 - 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. There was a direct correlation among FAS transcript level, FAS protein level, and FAS-mediated apoptotic sensitivity in the CTCL samples. When the FAS-deficient cell lines were transfected with a wild-type FAS construct, FAS expression and sensitivity to FAS-mediated apoptosis were restored. In aggregate, these findings provide evidence that like normal T cells, CTCL cells exhibit a mechanistic connection between transcriptional regulation of FAS and sensitivity to FAS-mediated apoptosis, point to the development of FAS deficiency as one molecular mechanism responsible for acquired resistance to apoptosis in CTCL, and indicate that upregulation of FAS expression can restore sensitivity to apoptosis.
AB - 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. There was a direct correlation among FAS transcript level, FAS protein level, and FAS-mediated apoptotic sensitivity in the CTCL samples. When the FAS-deficient cell lines were transfected with a wild-type FAS construct, FAS expression and sensitivity to FAS-mediated apoptosis were restored. In aggregate, these findings provide evidence that like normal T cells, CTCL cells exhibit a mechanistic connection between transcriptional regulation of FAS and sensitivity to FAS-mediated apoptosis, point to the development of FAS deficiency as one molecular mechanism responsible for acquired resistance to apoptosis in CTCL, and indicate that upregulation of FAS expression can restore sensitivity to apoptosis.
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U2 - 10.1038/jid.2008.309
DO - 10.1038/jid.2008.309
M3 - Article
C2 - 18923451
AN - SCOPUS:65249125807
SN - 0022-202X
VL - 129
SP - 1165
EP - 1173
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -