title: Synergistic targeted therapy for acute promyelocytic leukaemia: a model of translational research in human cancer.
abstract: Acute promyelocytic leukaemia (APL), the M3 subtype of acute myeloid leukaemia, was once a lethal disease, yet nowadays the majority of patients with APL can be successfully cured by molecularly targeted therapy. This dramatic improvement in the survival rate is an example of the advantage of modern medicine. APL is characterized by a balanced reciprocal chromosomal translocation fusing the promyelocytic leukaemia (PML) gene on chromosome 15 with the retinoic acid receptor α (RARα) gene on chromosome 17. It has been found that all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) alone exerts therapeutic effect on APL patients with the PML-RARα fusion gene, and the combination of both drugs can act synergistically to further enhance the cure rate of the patients. Here, we provide an insight into the pathogenesis of APL and the mechanisms underlying the respective roles of ATRA and ATO. In addition, treatments that lead to more effective differentiation and apoptosis of APL cells, including leukaemia-initiating cells, and more thorough eradication of the disease will be discussed. Moreover, as a model of translational research, the development of a cure for APL has followed a bidirectional approach of 'bench to bedside' and 'bedside to bench', which can serve as a valuable example for the diagnosis and treatment of other malignancies.
authors.affiliation: State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: J-Q
authors.initials: JQ
authors.lastname: Mi
authors.affiliation: State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: G-B
authors.initials: GB
authors.lastname: Zhou
authors.affiliation: Department of Hematology, the First Hospital of China Medical University, Shenyang, China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Yan
authors.affiliation: State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010087:Oxides / Q000494:pharmacology*; D057170:Translational Research, Biomedical; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D000077237:Arsenic Trioxide
keywords: acute promyelocytic leukaemia; all-trans retinoic acid; arsenic trioxide; synergistic targeting therapy