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Volume 30, Issue 4, Pages 415-426 (April 2006)


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A Fas agonist induces high levels of apoptosis in haematological malignancies

Peter Greaneya1, Aimable Nahimanab1, Lucienne Lagopoulosb, Anne-Lise Ettera, Dominique Aubryb, Antoine Attingera, Nicola Beltraminellia, Boris Hunia, Isabelle Bassia, Bernard Sordata, Stéphane Demotza, Marc Dupuisa, Michel A. DuchosalbCorresponding Author Informationemail address

Received 13 May 2005; accepted 8 August 2005.

Abstract 

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.

a Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland

b Service of Hematology, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland

Corresponding Author InformationCorresponding author. Tel.: +41 21 31 44215.

1 These authors contributed equally to the work.

PII: S0145-2126(05)00314-0

doi:10.1016/j.leukres.2005.08.006


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