title: Differential CD95 expression and function in T and B lineage acute lymphoblastic leukemia cells.
abstract: CD95 (Fas/APO-1) is a cell surface receptor able to trigger apoptosis in a variety of cell types. The expression and function of the CD95 antigen on leukemic blasts from 42 patients with B lineage and 53 patients with T lineage acute lymphoblastic leukemia (ALL) were investigated using immunofluorescence staining and apoptosis assays. The CD95 surface antigen was expressed in most ALL cases, with the T lineage ALL usually showing a higher intensity of surface CD95 expression as compared with the B lineage ALL cells (relative fluorescence intensity, RFI: 4.8 +/- 0.47 vs 2.2 +/- 0.23, respectively, P < 0.01). Functional studies disclosed that upon oligomerization by anti-CD95 monoclonal antibodies the CD95 protein was either not able to initiate apoptosis of leukemic cells (75% of cases) or induced low rates of apoptosis (20% of cases). Only in 5% of cases did the apoptosis rate exceed the 20% level of the CD95-specific apoptosis. Most of the CD95-sensitive cases were found among T lineage ALLs (38% of T lineage vs 10% of B lineage ALLs). Overall, the extent of CD95-induced apoptosis did not correlate with the expression level of CD95. Similarly, no significant correlation between expression level and functionality of CD95 in human leukemia cell lines of B and T cell origin could be observed. Bcl-2 protein has been associated with prolonged cell survival and has been shown to block partially CD95-mediated apoptosis, but for ALL cells no correlation between bcl-2 expression and spontaneous or CD95-mediated apoptosis could be found. The results obtained in this study indicate that, despite constitutive expression of CD95, the ALL cells are mainly resistant to CD95-triggering. More detailed investigations of the molecular mechanisms involved in the intracellular apoptotic signal transduction, such as interactions of the bcl-2 and the other members of the bcl-2 family, and functionality of the interleukin-1beta converting enzyme (ICE) like-proteases, may give new insights into key events responsible for the resistance or sensitivity to the induction of apoptosis in acute leukemia.
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Robert-Rössle Clinic, Humboldt University of Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Karawajew
authors.forename: C
authors.initials: C
authors.lastname: Wuchter
authors.forename: V
authors.initials: V
authors.lastname: Ruppert
authors.forename: H
authors.initials: H
authors.lastname: Drexler
authors.forename: H J
authors.initials: HJ
authors.lastname: Gruss
authors.forename: B
authors.initials: B
authors.lastname: Dörken
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000473:pathology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor