title: Triple A therapy: the molecular underpinnings of the unique sensitivity of leukemic promyelocytes to anthracyclines, all-trans-retinoic acid and arsenic trioxide.
abstract: If looking for a mnemonic to remember the relevant facts about acute promyelocytic leukemia (APL), one just has to remember that APL is a disease of A's. It is acute and it is highly sensitive to treatment with anthracyclines, all-trans-retinoic acid (RA) and arsenic trioxide (ATO). The presence of fusions involving the retinoic acid receptor alpha (RARA) is without question the central player driving APL and dictating the response of this disease to these therapeutic agents. However, beyond this knowledge, the molecular mechanisms that contribute to the complicated pathogenesis and the response to treatment of APL are not completely defined. As more is understood about this hematological malignancy, there are more opportunities to refine and improve treatment based on this knowledge. In this review article, we discuss the response of APL to these "A" therapies.
authors.affiliation: Division of Experimental Medicine, Department of Oncology, Segal Cancer Comprehensive Centre, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montréal, Quebec H3T 1E2, Canada.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Nichol
authors.affiliation: Division of Experimental Medicine, Department of Oncology, Segal Cancer Comprehensive Centre, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montréal, Quebec H3T 1E2, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Garnier
authors.affiliation: Division of Experimental Medicine, Department of Oncology, Segal Cancer Comprehensive Centre, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montréal, Quebec H3T 1E2, Canada. Electronic address: wmiller@ldi.jgh.mcgill.ca.
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
mesh_terms: D018943:Anthracyclines / Q000494:pharmacology / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015973:Gene Expression Regulation, Leukemic; D042381:Granulocyte Precursor Cells / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D001152:Arsenicals; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010087:Oxides; D059005:Topoisomerase II Inhibitors; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D000077237:Arsenic Trioxide
keywords: acute promyelocytic leukemia; all-trans-retinoic acid; anthracyclines; arsenic trioxide