A Fas agonist induces high levels of apoptosis in haematological malignancies

被引:35
作者
Greaney, P
Nahimana, A
Lagopoulos, L
Etter, AL
Aubry, D
Attinger, A
Beltraminelli, N
Huni, B
Bassi, I
Sordat, B
Demotz, S
Dupuis, M
Duchosal, MA
机构
[1] Univ Lausanne Hosp, CHU Vaudois, Serv Hematol, CH-1011 Lausanne, Switzerland
[2] Apoxis SA, CH-1004 Lausanne, Switzerland
关键词
apoptosis; cytotoxicity; Fas; haematological malignancies; cancer;
D O I
10.1016/j.leukres.2005.08.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (C) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:415 / 426
页数:12
相关论文
共 49 条
  • [1] Single versus double autologous stem-cell transplantation for multiple myeloma
    Attal, M
    Harousseau, JL
    Facon, T
    Guilhot, F
    Doyen, C
    Fuzibet, JG
    Monconduit, M
    Hulin, C
    Caillot, D
    Bouabdallah, R
    Voillat, L
    Sotto, JJ
    Grosbois, B
    Bataille, R
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (26) : 2495 - 2502
  • [2] Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma
    Barlogie, B
    Jagannath, S
    Vesole, DH
    Naucke, S
    Cheson, B
    Mattox, S
    Bracy, D
    Salmon, S
    Jacobson, J
    Crowley, J
    Tricot, G
    [J]. BLOOD, 1997, 89 (03) : 789 - 793
  • [3] GENE-MARKING TO TRACE ORIGIN OF RELAPSE AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION
    BRENNER, MK
    RILL, DR
    MOEN, RC
    KRANCE, RA
    MIRRO, J
    ANDERSON, WF
    IHLE, JN
    [J]. LANCET, 1993, 341 (8837) : 85 - 86
  • [4] CD40-activated B-cell chronic lymphocytic leukemia cells for tumor immunotherapy: Stimulation of allogeneic versus autologous T cells generates different types of effector cells
    Buhmann, R
    Nolte, A
    Westhaus, D
    Emmerich, B
    Hallek, M
    [J]. BLOOD, 1999, 93 (06) : 1992 - 2002
  • [5] Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis
    Contri, A
    Brunati, AM
    Trentin, L
    Cabrelle, A
    Miorin, M
    Cesaro, L
    Pinna, LA
    Zambello, R
    Semenzato, G
    Donella-Deana, A
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (02) : 369 - 378
  • [6] Drug resistance does not correlate with resistance to Fas-mediated apoptosis
    Cullen, KV
    Davey, RA
    Davey, MW
    [J]. LEUKEMIA RESEARCH, 2001, 25 (01) : 69 - 75
  • [7] de Vries EGE, 2003, DRUGS TODAY, V39, P95
  • [8] Death receptors in chemotherapy and cancer
    Debatin, KM
    Krammer, PH
    [J]. ONCOGENE, 2004, 23 (16) : 2950 - 2966
  • [9] GENETIC MARKING SHOWS THAT PH(+) CELLS PRESENT IN AUTOLOGOUS TRANSPLANTS OF CHRONIC MYELOGENOUS LEUKEMIA (CML) CONTRIBUTE TO RELAPSE AFTER AUTOLOGOUS BONE-MARROW IN CML
    DEISSEROTH, AB
    ZU, ZF
    CLAXTON, D
    HANANIA, EG
    FU, SQ
    ELLERSON, D
    GOLDBERG, L
    THOMAS, M
    JANICEK, K
    ANDERSON, WF
    HESTER, J
    KORBLING, M
    DURETT, A
    MOEN, R
    BERENSON, R
    HEIMFELD, S
    HAMER, J
    CALVERT, L
    TIBBITS, P
    TALPAZ, M
    KANTARJIAN, H
    CHAMPLIN, R
    READING, C
    [J]. BLOOD, 1994, 83 (10) : 3068 - 3076
  • [10] Dick JE, 1997, STEM CELLS, V15, P204