Blood‐soluble Fas/APO‐1 (CD95) in chronic lymphocytic leukemia

To the Editor: The cell surface receptor protein Fas/APO-1 (CD95) may mediate apoptosis upon stimulation with its natural ligand (1). A soluble form (sFas) protects cells from apoptosis (2). Leukemic cells from patients with chronic lymphocytic leukemia (CLL) have been regarded as anti-apoptotic in character (3). The Fas antigen has been reported to be expressed in a minority (541%) of leukemic cells in 10/21 CLL patients (4). Nevertheless, increased sFaslAP0-1 concentrations have been recorded in CLL (5,6). It has been speculated that production of sFas/APO-1 in combination with shedding of other molecules, such as CD54, might provide tumor cells with a mechanism to escape immunosurveillance and apoptosis (6). Experiments carried out in vitro have demonstrated that a soluble form of the Fas molecule may protect cells from Fas-mediated apoptosis (2). In order to clarify the possible role of sFas/APO1 in the pathogenesis of CLL, we have determined the concentrations of blood sFas/APO-1 in 42 CLL patients and in 25 age-matched control subjects. The correlations between sFas concentrations and various clinical-hematological parameters were investigated. Blood samples were obtained after informed consent from 42 patients referred to the CLL outpatient clinic of Tampere University Hospital. The diagnosis and staging of CLL were based on standard clinical, morphological and immunophenotyping criteria (7). All patients had the B-cell phenotype. The Matutes CLL score ranged from 3 to 5. Blood samples were also obtained from 25 age-matched healthy control subjects. sFas/APO-1 ELISA. Circulating concentrations of sFas were assessed by an ELISA based on the use of horseradish peroxidase-conjugated antihuman Fas mouse-monoclonal antibody as described in detail previously (8). The detection limit is 0.01 pg/l and the lower limit of assay linearity 0.05 pg/l. Either serum or plasma was used. This assay gives identical sFas values in both plasma and serum samples (M.S., unpublished results). The mean serum/plasma sFas concentration in samples from 42 CLL patients was 3.52 k 1.33 pg/l (meanfSD, range 1.54-6.72 pg/l, Fig. 1). The corresponding mean sFas concentration in 25 agematched healthy subjects was 3.14k0. 69 pgA(1.834.83 pg/l, Fig. 1). The difference is not statistically significant (p > 0.05, t-test for independent values). There was a statistically significant correlation (Pearson product-moment correlation: r = 0.45, p = 0.0026, N = 42) between patient age and sFas concentration among our CLL patients. The same trend, although not statistically significant, was also observed among the control subjects (not shown). Interestingly, the serum/plasma sFas levels were not significantly correlated with the patients' sex, FAB phenotype, immunophenotype, bone marrow histology, progression velocity or Binet's stage (ANOVA). There was a slight negative correlation between blood lymphocyte count and sFas (Y= -0.43, p = 0.0044, N = 42). No correlations were noted between serum/plasma sFas concentrations and blood creatinine or alanine aminotransferase among the CLL patients (data not shown) or healthy control subjects. Our results revealed approximately similar serum/plasma sFas concentrations in CLL patients and age-matched healthy control subjects. Diseases known to increase blood sFas levels, such as