Resistance to APO-1 (CD95) induced apoptosis in T-ALL is determined by a BCL-2 independent anti-apoptotic program
Selective induction of programmed cell death, apoptosis, may represent a new approach to the treatment of cancer. Apoptosis can be induced by the monoclonal antibody anti-APO-1 directed against the cell surface receptor APO-1, a member of the nerve growth factor (NGF) receptor/tumor necrosis factor (TNF) receptor superfamily. We determined APO-1 expression and sensitivity to anti-APO-1 mediated apoptosis in childhood acute lymphoblastic leukemia cells of T lymphocyte precursor phenotype (T-ALL). APO-1 was constitutively expressed by 21 of 30 T-ALL and by all T-ALL cell lines investigated. However, most APO-1 positive T-ALL were resistant to anti-APO-1 mediated apoptosis. Sensitivity to anti-APO-1 mediated apoptosis was independent of the density of APO-1 expression on the cell surface and independent of the amount of Bcl-2. Incubation of resistant T-ALL with the protein synthesis inhibitor cycloheximide reversed resistance and induced sensitivity to anti-APO-1 mediated apoptosis in most T-ALL. These data suggest that resistance to anti-APO-1 mediated apoptosis in T-ALL is maintained by an active cellular program. Reversion of resistance to sensitivity towards induction of apoptosis in tumors may provide a new basis for successful therapeutic intervention.
Medienart: |
Artikel |
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Erscheinungsjahr: |
1995 |
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Erschienen: |
1995 |
Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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Enthalten in: |
Leukemia - 9(1995), 5 vom: 11. Mai, Seite 815-20 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Debatin, K M [VerfasserIn] |
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Anmerkungen: |
Date Completed 06.07.1995 Date Revised 16.11.2017 published: Print Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM075156784 |
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100 | 1 | |a Debatin, K M |e verfasserin |4 aut | |
245 | 1 | 0 | |a Resistance to APO-1 (CD95) induced apoptosis in T-ALL is determined by a BCL-2 independent anti-apoptotic program |
264 | 1 | |c 1995 | |
336 | |a Text |b txt |2 rdacontent | ||
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500 | |a Date Completed 06.07.1995 | ||
500 | |a Date Revised 16.11.2017 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Selective induction of programmed cell death, apoptosis, may represent a new approach to the treatment of cancer. Apoptosis can be induced by the monoclonal antibody anti-APO-1 directed against the cell surface receptor APO-1, a member of the nerve growth factor (NGF) receptor/tumor necrosis factor (TNF) receptor superfamily. We determined APO-1 expression and sensitivity to anti-APO-1 mediated apoptosis in childhood acute lymphoblastic leukemia cells of T lymphocyte precursor phenotype (T-ALL). APO-1 was constitutively expressed by 21 of 30 T-ALL and by all T-ALL cell lines investigated. However, most APO-1 positive T-ALL were resistant to anti-APO-1 mediated apoptosis. Sensitivity to anti-APO-1 mediated apoptosis was independent of the density of APO-1 expression on the cell surface and independent of the amount of Bcl-2. Incubation of resistant T-ALL with the protein synthesis inhibitor cycloheximide reversed resistance and induced sensitivity to anti-APO-1 mediated apoptosis in most T-ALL. These data suggest that resistance to anti-APO-1 mediated apoptosis in T-ALL is maintained by an active cellular program. Reversion of resistance to sensitivity towards induction of apoptosis in tumors may provide a new basis for successful therapeutic intervention | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
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650 | 7 | |a Receptors, Cell Surface |2 NLM | |
650 | 7 | |a fas Receptor |2 NLM | |
700 | 1 | |a Krammer, P H |e verfasserin |4 aut | |
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