@article{92f44978f7504576b50b3339bbdababb,
title = "Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia",
abstract = "BCL-2 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",
author = "Marina Konopleva and Rooha Contractor and Twee Tsao and Ismael Samudio and Ruvolo, {Peter P.} and Shinichi Kitada and Xingming Deng and Dayong Zhai and Shi, {Yue Xi} and Thomas Sneed and Monique Verhaegen and Maria Soengas and Ruvolo, {Vivian R.} and Teresa McQueen and Schober, {Wendy D.} and Watt, {Julie C.} and Tilahun Jiffar and Xiaoyang Ling and Marini, {Frank C.} and David Harris and Martin Dietrich and Zeev Estrov and James McCubrey and May, {W. Stratford} and Reed, {John C.} and Michael Andreeff",
note = "Funding Information: Supported by grants from the National Cancer Institute (PO1 CA55164) and the Paul and Mary Haas Chair in Genetics (to M.A.), and the Commonwealth Cancer Foundation for Research (to M.K.). The authors wish to thank Drs. S. Rosenberg, S. Elmore, and S. Fesik from Abbott Laboratories for the material and for stimulating discussions; and Dr. Z. Huang from The Burnham Institute for Medical Research for preparation of FITC-BIM peptide. The authors thank Rosemarie Lauzon and Leslie Calvert for excellent administrative assistance. ",
year = "2006",
month = nov,
doi = "10.1016/j.ccr.2006.10.006",
language = "English (US)",
volume = "10",
pages = "375--388",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}