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

  • Y. Jing
  • S. Waxman
Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

Acute Myeloid Leukemia Retinoic Acid HDAC Inhibitor Arsenic Trioxide Gemtuzumab Ozogamicin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Y. Jing
    • 1
  • S. Waxman
    • 1
  1. 1.Division of Hematology/Oncology, Department of MedicineMount Sinai School of MedicineNew YorkUSA

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