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Acute Promyelocytic Leukemia pp 245–269Cite as

The Design of Selective and Non-selective Combination Therapy for Acute Promyelocytic Leukemia

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 313))

Abstract

Acute promyelocytic leukemia (APL) is an unique subtype of acute myeloid leukemia typically carrying a specific reciprocal chromosome translocation, t(15;17), leading to the expression of a leukemia-generating fusion protein, PML-RARα. APL patients are responsive to APL-selective reagents such as all-trans retinoic acid (ATRA) or arsenic trioxide and non-selective cytotoxic chemotherapy. Nearly all de novo APL patients undergo clinical remission when treated with ATRA plus chemotherapy or with the combinational selective therapy, ATRA plus As2O3. Combining ATRA with As2O3 as an induction followed by chemotherapy consolidation results in more profound clinical remissions compared to treatment with any agent alone or any of the other possible combinations. The mechanism of action of each of these agents differs. ATRA induces APL cell differentiation and PML-RARα proteolysis. As2O3 induces APL cell partial differentiation, PML-RARα proteolysis, and apoptosis. Chemotherapy, mainly using anthracyclines, induces APL cell death. The combined effects of selective APL therapy (ATRA and As2O3) and/or non-selective chemotherapy in APL cells in vitro and their mechanisms in relation to clinical protocol design are discussed.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1178, New York, NY, 10029-6547, USA

    Y. Jing & S. Waxman

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  1. Y. Jing
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  2. S. Waxman
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  1. Memorial Sloan-Kettering Cancer Center, Sloan-Kettering-Institute, 1275 York Avenue, New York, New York, 10021, USA

    Pier Paolo Pandolfi MD, Ph.D.

  2. The Scripps Research Institute, 10550 North Torreye Pines Road, La Jolla, CA, 92037, USA

    Peter K. Vogt Ph.D.

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Jing, Y., Waxman, S. (2007). The Design of Selective and Non-selective Combination Therapy for Acute Promyelocytic Leukemia. In: Pandolfi, P.P., Vogt, P.K. (eds) Acute Promyelocytic Leukemia. Current Topics in Microbiology and Immunology, vol 313. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-34594-7_13

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