Clinical Importance of Circulating and Cellular Expression Levels of Fas and Fas Ligand in Pediatric Patients With Lymphoproliferative Malignancies

Abstract

Objectives of this study were to determine the extend of soluble Fas (sFas) and soluble FasL (sFasL) at the time of diagnosis and to evaluate its prognostic relevance under chemotherapy in childhood lymphoproliferative malignancies. The authors measured the circulating sFas and sFasL by ELISA in 25 children with newly diagnosed either ALL or NHL, as well as their expression of Fas and FasL at the time of diagnosis and remission. They did not observe any statistically significant difference between the patient group and age-matched healthy controls for sFas levels, whereas sFasL concentration in study population at the time of diagnosis was significantly higher than that in control subjects (1.05 +/- 1.46 vs. 0.36 +/- 0.18 ng/mL, p = .024). At remission the authors observed a significant decrease in the sFasL levels of all patients whose sFasL concentrations were above the minimal detectable level at the time of diagnosis (p = .008). sFasL and Fas/FasL immunohistochemical staining did not have an effect on survival. sFasL may be a marker in monitoring complete remission in children with LPM.

Soluble CD95L in cancers and chronic inflammatory disorders, a new therapeutic target?

“…Contradicting this initial study, a prospective analysis on childhood lymphoproliferative malignancies, including 18 ALLs and 7 non-Hodgkin lymphomas (NHLs) patients revealed a significant increase in s-CD95L concentration [64]. Moreover, patients with elevated s-CD95L levels exhibited a detrimental effect on relapse-free survival (RFS) and overall survival (OS) [64]. This discrepancy could be explained by the cancer stage and also by the comparison of patients at diagnosis or in the course of the treatment.…”

“…In contrast, no trace of this ligand has been found in adult T-cell leukemia (ATL), acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL) or acute lymphocytic leukemia (ALL) [63]. Contradicting this initial study, a prospective analysis on childhood lymphoproliferative malignancies, including 18 ALLs and 7 non-Hodgkin lymphomas (NHLs) patients revealed a significant increase in s-CD95L concentration [64]. Moreover, patients with elevated s-CD95L levels exhibited a detrimental effect on relapse-free survival (RFS) and overall survival (OS) [64].…”