Increased serum levels of soluble Fas in progressive B-CLL.
Clinical progression of B-cell chronic lymphocytic leukemia (B-CLL) depends on survival and accumulation of leukemic cells, regulated in part by physical cell contact and soluble molecules. Here we have studied the Fas/FasL system in relation to clinical progression in B-CLL. Serum levels of soluble Fas (sFas) and FasL (sFasL) were determined by ELISA in 43 progressive and 40 non-progressive B-CLL patients and in 21 control individuals. Correlation between sFas serum levels and clinical progression, stage and survival were statistically analyzed. We found high levels of sFas in B-CLL sera correlated with disease progression (p<0.01). In addition, higher sFas levels were found in patients in stages II, III and IV in comparison to patients in stage 0 (p<0.05, p<0.01, p<0.03, respectively). Survival was significantly shorter for patients with > or =6 ng/ml sFas serum levels, although a multivariate analysis did not show sFas to be a significant independent prognostic factor. Fresh B-CLL cells showed only low levels of membrane expression, which were not correlated to sFas levels in serum. In vitro activation of B-CLL cells increased Fas expression, as reported earlier, and induced cells to release sFas into the supernatant. In conclusion, our results indicate that sFas in serum may be a useful parameter for the prediction of clinical progression in B-CLL.
Osorio
L M
LM
Microbiology and Tumor Biology Center, Karolinska Institute, Department of Hematology, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. lydoso@ki.se
Aguilar-Santelises
M
M
De Santiago
A
A
Hachiya
T
T
Mellstedt
H
H
Jondal
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D019014:fas Receptor / Q000097:blood*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor