The Bcl-2 family of antiapoptotic and proapoptotic proteins serve as key regulators of the mitochondrial pathway of apoptosis. Multiple signals from a variety of cell death stimuli converge upon mitochondria to trigger the intrinsic apoptotic cascade. Bcl-2 family proteins are intimately related to prognosis and therapeutic resistance in acute myeloid leukemia (AML), making them rational targets for drug development. Also, directly targeting Bcl-2 family proteins circumvents many of the problems associated with targeting upstream molecules. The Bcl-2 antisense oligonucleotide oblimersen failed to live up to its initial promise in large phase III trials. The discovery of ABT-737, a novel, small-molecule inhibitor of specific protein–protein interactions, gave a much-needed impetus to the field of “BH3 mimetic” research. The demonstration that Mcl-1, an antiapoptotic Bcl-2 family protein that is not inhibited by ABT-737 or its analogs, is of crucial importance in AML, underscores the need for rational drug combinations that simultaneously target multiple arms of the apoptotic regulatory machinery.
CITATION STYLE
Bose, P., & Grant, S. (2015). Bcl-2 family: Translational aspects. In Targeted Therapy of Acute Myeloid Leukemi (pp. 151–173). Springer New York. https://doi.org/10.1007/978-1-4939-1393-0_4
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