A Fas agonist induces high levels of apoptosis in haematological malignancies.
We developed and tested a potent hexameric Fas agonist, termed MegaFasL, for its cytotoxic effects on a panel of human haematopoietic malignant cells and healthy human haematopoietic progenitor cells (CD34+CD38low). Results demonstrated that MegaFasL induced apoptosis in cell lines and primary cells representing multiple myeloma (MM), acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and Burkitt's lymphoma. Cells from a chronic myeloid leukaemia (CML) line and from patients with chronic lymphocytic leukaemia (CLL) were resistant. Furthermore, CD34+CD38low progenitor cells were also resistant to MegaFasL. The data indicate that MegaFasL could be a highly efficient therapeutic agent ex vivo or potentially in vivo.
Greaney
Peter
P
Apoxis S.A., 18-20 Avenue de Sévelin, 1004 Lausanne, Switzerland.
Nahimana
Aimable
A
Lagopoulos
Lucienne
L
Etter
Anne-Lise
AL
Aubry
Dominique
D
Attinger
Antoine
A
Beltraminelli
Nicola
N
Huni
Boris
B
Bassi
Isabelle
I
Sordat
Bernard
B
Demotz
Stéphane
S
Dupuis
Marc
M
Duchosal
Michel A
MA
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D019337:Hematologic Neoplasms / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D019014:fas Receptor / Q000187:drug effects*
D019014:fas Receptor; D020169:Caspases