Title of article
Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia
Author/Authors
Konopleva، نويسنده , , Marina and Contractor، نويسنده , , Rooha and Tsao، نويسنده , , Twee and Samudio، نويسنده , , Ismael and Ruvolo، نويسنده , , Peter P. and Kitada، نويسنده , , Shinichi and Deng، نويسنده , , Xingming and Zhai، نويسنده , , Dayong and Shi، نويسنده , , Yue-Xi and Sneed، نويسنده , , Thomas and Verhaegen، نويسنده , , Monique and Soengas، نويسنده , , Maria and Ruvolo، نويسنده , , Vivian R. and McQueen، نويسنده , , Teresa and Schober، نويسنده , , Wendy D. and Watt، نويسنده , , Julie C. and Jiffar، نويسنده , , Tilahun and Ling، نويسنده , , Xiaoyang and Marini، نويسنده , , Frank C. and Harris، نويسنده , , David E. Dietrich، نويسنده , , Martin and Estrov، نويسنده , , Zeev and McCubrey، نويسنده , , James and May، نويسنده , , W. Stratford and Reed، نويسنده , , John C. and Andreeff، نويسنده , , Michael، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2006
Pages
14
From page
375
To page
388
Abstract
Summary
proteins are critical for cell survival and are overexpressed in many tumors. ABT-737 is a small-molecule BH3 mimetic that exhibits single-agent activity against lymphoma and small-cell lung cancer in preclinical studies. We here report that ABT-737 effectively kills acute myeloid leukemia blast, progenitor, and stem cells without affecting normal hematopoietic cells. ABT-737 induced the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway. In cells with phosphorylated BCL-2 or increased MCL-1, ABT-737 was inactive. Inhibition of BCL-2 phosphorylation and reduction of MCL-1 expression restored sensitivity to ABT-737. These data suggest that ABT-737 could be a highly effective antileukemia agent when the mechanisms of resistance identified here are considered.
Keywords
CELLCYCLE
Journal title
Cancer Cell
Serial Year
2006
Journal title
Cancer Cell
Record number
1336324
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