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Bcl-2 Family: Translational Aspects

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Book cover Targeted Therapy of Acute Myeloid Leukemia

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

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.

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Acknowledgments

This work was supported in part by the following awards to Dr. Grant: RO1 CA093738, RO1 CA100866, P50 CA130805, P50 CA142509, and RC2 CA148431 from the National Institutes of Health, and award #6181–10 from the Leukemia and Lymphoma Society.

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  1. Massey Cancer Center, Virginia Commonwealth University, 1201 E Marshall St, MMEC -11th floor, Room 213, P.O. Box 980070, 23298, Richmond, VA, USA

    Prithviraj Bose M.D.

  2. Division of Hematology and Oncology, Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Box 980035, Richmond, VA 23298, USA

    Dr. Steven Grant

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  1. Prithviraj Bose M.D.
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Correspondence to Prithviraj Bose M.D. .

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  1. Dept. Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Michael Andreeff

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Bose, P., Grant, S. (2015). Bcl-2 Family: Translational Aspects. In: Andreeff, M. (eds) Targeted Therapy of Acute Myeloid Leukemia. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1393-0_4

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