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Blood, 1 October 2001, Vol. 98, No. 7, pp. 2183-2192
NEOPLASIA
Apo2L/TRAIL and Bcl-2-related proteins regulate type I
interferon-induced apoptosis in multiple myeloma
Quan Chen,
Bendi Gong,
Ashraf S. Mahmoud-Ahmed,
Aimin Zhou,
Eric D. Hsi,
Mohamad Hussein, and
Alexandru Almasan
From the Department of Cancer Biology, Lerner Research
Institute; the Department of Clinical Pathology; the Myeloma Program;
the Department of Radiation Oncology; the Taussig Cancer Center; and
The Cleveland Clinic Foundation, Cleveland, OH.
It has been reported that interferons (IFNs) may have antitumor
activity in multiple myeloma (MM). The mechanism for their effect on
MM, however, remains elusive. This study shows that IFN- and - ,
but not - , induce apoptosis characterized by Annexin V positivity,
nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from
10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one
of the earliest events following IFN administration in U266 cells.
Treatment of these cells with TRAIL, but not with Fas agonistic
antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in
U266 cells was partially blocked by a dominant-negative Apo2L receptor,
DR5, demonstrating the functional significance of Apo2L induction. This
study shows that IFNs activate caspases and the mitochondrial-dependent
apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-
and - induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late,
amplified cytochrome c release coincides with changes in levels of
Bcl-2, Bcl-XL, and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of
Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs
and Apo2L induce cell death of CD38+/CD45 /dim
plasma cells, without significant effect on nonplasma blood cells, in a
caspase and Bcl-2 cleavage-dependent manner. These results warrant
further clinical studies with IFNs and Apo2L in MM.
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|
|
|
|
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986 - 994.
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|
|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Secchiero, A. Gonelli, P. Mirandola, E. Melloni, L. Zamai, C. Celeghini, D. Milani, and G. Zauli
Tumor necrosis factor-related apoptosis-inducing ligand induces monocytic maturation of leukemic and normal myeloid precursors through a caspase-dependent pathway
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100(7):
2421 - 2429.
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[Full Text]
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|
|
|
|
|
|
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J. Biol. Chem.,
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277(32):
28504 - 28511.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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169(2):
847 - 855.
[Abstract]
[Full Text]
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|
|
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