Low FAS/CD95 Expression in CTCL Correlates with Reduced Sensitivity to Apoptosis

Strategic Insights -

CTCL (cutaneous T-cell lymphoma) cells show a low expression of FAS/CD95, which correlates with reduced sensitivity to apoptosis. This phenomenon can be restored by upregulating FAS expression, according to a study published in the Journal of Investigative Dermatology. The research team, led by J. Wu from the University of Wisconsin, found that 30 out of 31 CTCL cases and 5 out of 6 large plaque parapsoriasis cases exhibited low FAS expression. This low expression was confirmed in four CTCL lines, a patient with SS, an acute lymphoblastic leukemia T-cell line, and JFL, a FAS-low variant of Jurkat. The study suggests that upregulating FAS expression can restore sensitivity to apoptosis in CTCL cells.

Key Takeaways:

  • The study found that CTCL cells exhibit low FAS/CD95 expression, which correlates with reduced sensitivity to apoptosis.
  • 30 out of 31 CTCL cases and 5 out of 6 large plaque parapsoriasis cases exhibited low FAS expression.
  • Four CTCL lines, a patient with SS, an acute lymphoblastic leukemia T-cell line, and JFL, a FAS-low variant of Jurkat, were found to have low FAS expression.
  • The study confirmed a direct correlation between FAS transcript level, FAS protein level, and FAS-mediated apoptotic sensitivity in CTCL samples.
  • Transfection of FAS-deficient cell lines with a wild-type FAS construct restored FAS expression and sensitivity to FAS-mediated apoptosis.
  • The study suggests that upregulating FAS expression can restore sensitivity to apoptosis in CTCL cells.
  • CTCL cells exhibit a mechanistic connection between transcriptional regulation of FAS and sensitivity to FAS-mediated apoptosis similar to normal T cells.
  • FAS deficiency development is one molecular mechanism responsible for acquired resistance to apoptosis in CTCL.

Statistics:

  • 30 out of 31 CTCL cases exhibited low FAS expression.
  • 5 out of 6 large plaque parapsoriasis cases exhibited low FAS expression.
  • Four CTCL lines, a patient with SS, an acute lymphoblastic leukemia T-cell line, and JFL, a FAS-low variant of Jurkat, were found to have low FAS expression.
  • 31 CTCL samples showed a direct correlation between FAS transcript level, FAS protein level, and FAS-mediated apoptotic sensitivity.
  • 4 FAS-deficient cell lines were transfected with a wild-type FAS construct, restoring FAS expression and sensitivity to FAS-mediated apoptosis.

Sources:

  • J. Wu et al., "Low FAS/CD95 expression by CTCL correlates with reduced sensitivity to apoptosis that can be restored by FAS upregulation," Journal of Investigative Dermatology, 2009;129(5):1165-73.
  • Blood Weekly, "Scientists Discuss New Findings in Apoptosis," 2009.