A Fas agonist induces high levels of apoptosis in haematological malignancies

Greaney, Peter; Nahimana, Aimable; Lagopoulos, Lucienne; Etter, Anne-Lise; Aubry, Dominique; Attinger, Antoine; Beltraminelli, Nicola; Huni, Boris; Bassi, Isabelle; Sordat, Bernard; Demotz, Stéphane; Dupuis, Marc; Duchosal, Michel A.

doi:10.1016/j.leukres.2005.08.006

« Previous Next »Leukemia Research
Volume 30, Issue 4 , Pages 415-426, April 2006

A Fas agonist induces high levels of apoptosis in haematological malignancies

Peter Greaney
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
- These authors contributed equally to the work.
Aimable Nahimana
- Service of Hematology, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland
- These authors contributed equally to the work.
Lucienne Lagopoulos
- Service of Hematology, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland
Anne-Lise Etter
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Dominique Aubry
- Service of Hematology, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland
Antoine Attinger
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Nicola Beltraminelli
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Boris Huni
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Isabelle Bassi
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Bernard Sordat
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Stéphane Demotz
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Marc Dupuis
- Apoxis S.A., 18–20 Avenue de Sévelin, 1004 Lausanne, Switzerland
Michel A. Duchosal
- Service of Hematology, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland
- Corresponding author. Tel.: +41 21 31 44215.

Received 13 May 2005; accepted 8 August 2005. published online 07 March 2011.

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.

Abbreviations: 7AAD, 7-aminoactinomycin D, ALL, acute lymphoblastic leukaemia, AML, acute myeloid leukaemia, CLL, chronic lymphocytic leukaemia, CML, chronic myeloid leukaemia, FCS, fetal calf serum, IC₅₀, inhibitory concentration of 50% of cells, MFI, mean fluorescence intensity, MM, multiple myeloma, PESMTS, phenazyne etho sulfate 4(4,5-dimethylthiazol-carboxymethoxyphenyl)-2(4-sulfophenyl) 2H tetrazolium, PI, propidium iodide, sFasL, soluble Fas ligand, sFasL M2, crosslinked soluble Fas ligand