Advances in therapies for acute promyelocytic leukemia

Cancer Sci. 2011 Nov;102(11):1929-37. doi: 10.1111/j.1349-7006.2011.02045.x. Epub 2011 Aug 24.

Abstract

Acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia (AML), results from the arrest of the maturation of hematopoietic progenitors at the promyelocyte stage. It has been shown that APL is associated with a reciprocal chromosomal translocation, involving chromosomes 15 and 17, which fuses the gene encoding the retinoic acid receptor α (RARα) and the promyelocytic leukemia (PML) gene. The resultant PML-RARα fusion protein plays a critical role in the pathogenesis of APL. Although there are many subtypes of AML, all are typically managed using a standard chemotherapy regimen of an anthracycline plus cytarabine arabinoside (CA). Despite high rates of complete remission following standard chemotherapy, most patients relapse and long-term disease-free survival is only 30-40%. The introduction of drugs such as all-trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML-RARα fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. The purposes of the present review are to provide the latest results and future directions of clinical research into APL and to illustrate how new therapies, such as ATRA plus anthracycline-based induction and consolidation therapy, risk-adapted therapy, salvage therapy containing arsenic trioxide-based regimens, and hematopoietic stem cell transplantation, have improved the treatment outcomes for APL patients.

Publication types

  • Review

MeSH terms

  • Anthracyclines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arsenic Trioxide
  • Arsenicals / administration & dosage
  • Arsenicals / pharmacology
  • Cell Differentiation / drug effects
  • Clinical Trials as Topic
  • Consolidation Chemotherapy / trends*
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Leukemic / drug effects
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Induction Chemotherapy / trends*
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / surgery
  • Maintenance Chemotherapy / trends*
  • Multicenter Studies as Topic
  • Oncogene Proteins, Fusion / antagonists & inhibitors
  • Oncogene Proteins, Fusion / physiology
  • Oxides / administration & dosage
  • Oxides / pharmacology
  • Risk
  • Salvage Therapy
  • Tretinoin / administration & dosage
  • Tretinoin / adverse effects
  • Tretinoin / pharmacology

Substances

  • Anthracyclines
  • Arsenicals
  • Oncogene Proteins, Fusion
  • Oxides
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Cytarabine
  • Tretinoin
  • Arsenic Trioxide