APO-1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bcl-2 oncogene expression.
We studied induction of apoptosis in several human malignant B cells from chronic lymphocytic leukemias (BCLL) by triggering the APO-1 antigen. The APO-1 antigen was found to be expressed on the surface of malignant B cells. In BCLL cells from most patients, APO-1 antigen expression increased following in vitro activation by Staphylococcus aureus Cowan I (SAC) or interleukin-2 (IL-2). In certain cases of BCLL co-stimulation with SAC plus IL-2 resulted in a synergistic up-regulation of the APO-1 antigen on the cell surface and prepared BCLL cells for monoclonal antibody anti-APO-1 mediated apoptosis. Interestingly, bcl-2 mRNA expression decreased upon stimulation with SAC plus IL-2, whereas SAC or IL-2 alone did not affect the level of bcl-2 expression. Thus, in these BCLL cells induction of anti-APO-1-mediated apoptosis appeared to be correlated with bcl-2 mRNA down-regulation. One informative BCLL, however, with a similar pattern of APO-1-antigen expression, did not show SAC plus IL-2-dependent bcl-2 down-regulation. Surprisingly, these cells proliferated in response to anti-APO-1 only when cells were co-stimulated with SAC plus IL-2. Our data suggest that down-regulation of bcl-2 prepares BCLL cells for induction of APO-1-mediated apoptosis. In addition they demonstrate that triggering of the APO-1 antigen may also lead to the induction of proliferation in special cases of BCLL.
Mapara
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Robert Rössle Klinik, Max Delbrück Centrum für Molekulare Medizin, Universitäts Klinikum Rudolf Virchow-Freie Universität Berlin, FRG.
Bargou
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Zugck
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Döhner
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Ustaoglu
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Jonker
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Krammer
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Dörken
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D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000503:physiopathology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019014:fas Receptor
D000954:Antigens, Surface; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019014:fas Receptor