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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2246-2253
NEOPLASIA
CGP57148B (STI-571) induces
differentiation and apoptosis and sensitizes Bcr-Abl-positive human
leukemia cells to apoptosis due to antileukemic drugs
Guofu Fang,
Caryn Naekyung Kim,
Charles L. Perkins,
Nimmanapalli Ramadevi,
Elliott Winton,
Sylvie Wittmann, and
Kapil N. Bhalla
From the H. Lee Moffitt Cancer Center and Research
Institute, University of South Florida, Tampa, FL; and Emory University
School of Medicine, Atlanta, GA.
The differentiation and apoptosis-sensitizing effects of the
Bcr-Abl-specific tyrosine kinase inhibitor CGP57148B, also known as
STI-571, were determined in human Bcr-Abl-positive HL-60/Bcr-Abl and
K562 cells. First, the results demonstrate that the ectopic expression
of the p185 Bcr-Abl fusion protein induced hemoglobin in the acute
myeloid leukemia (AML) HL-60 cells. Exposure to low-dose cytosine
arabinoside (Ara-C; 10 nmol/L) increased hemoglobin levels in
HL-60/Bcr-Abl and in the chronic myeloid leukemia (CML) blast crisis
K562 cells, which express the p210 Bcr-Abl protein. As compared with
HL-60/neo, HL-60/Bcr-Abl and K562 cells were resistant to apoptosis
induced by Ara-C, doxorubicin, or tumor necrosis factor- (TNF- ),
which was associated with reduced processing of caspase-8 and Bid
protein and decreased cytosolic accumulation of cytochrome c (cyt c).
Exposure to CGP57148B alone increased hemoglobin levels and CD11b
expression and induced apoptosis of HL-60/Bcr-Abl and K562 cells.
CGP57148B treatment down-regulated antiapoptotic XIAP, cIAP1, and
Bcl-xL, without affecting Bcl-2, Bax, Apaf-1, Fas (CD95),
Fas ligand, Abl, and Bcr-Abl levels. CGP57148B also inhibited
constitutively active Akt kinase and NF B in Bcr-Abl-positive cells.
Attenuation of NF B activity by ectopic expression of transdominant
repressor of I B sensitized HL-60/Bcr-Abl and K562 cells to TNF-
but not to apoptosis induced by Ara-C or doxorubicin.
Importantly, cotreatment with CGP57148B significantly increased
Ara-C- or doxorubicin-induced apoptosis of HL-60/Bcr-Abl and
K562 cells. This was associated with greater cytosolic accumulation of
cyt c and PARP cleavage activity of caspase-3. These in vitro data
indicate that combinations of CGP57148B and antileukemic drugs such as
Ara-C may have improved in vivo efficacy against Bcr-Abl-positive
acute leukemia.

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[Full Text]
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|
 |
|

|
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|
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|
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|
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|
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101(8):
3236 - 3239.
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[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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100(2):
443 - 448.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Acute Myeloid Leukemia and Acute Promyelocytic Leukemia
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January 1, 2003;
2003(1):
82 - 101.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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November 15, 2002;
100(10):
3731 - 3740.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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October 15, 2002;
62(20):
5761 - 5769.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Flavopiridol Potentiates STI571-induced Mitochondrial Damage and Apoptosis in BCR-ABL-positive Human Leukemia Cells
Clin. Cancer Res.,
September 1, 2002;
8(9):
2976 - 2984.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation
Blood,
May 15, 2002;
99(10):
3792 - 3800.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Modulation of p210BCR-ABL activity in transduced primary human hematopoietic cells controls lineage programming
Blood,
May 1, 2002;
99(9):
3197 - 3204.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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