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Synergistic targeted therapy for acute promyelocytic leukaemia: a model of translational research in human cancer
Author(s) -
Mi J.Q.,
Chen S.J.,
Zhou G.B.,
Yan X.J.,
Chen Z.
Publication year - 2015
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12376
Subject(s) - arsenic trioxide , medicine , acute promyelocytic leukemia , cancer research , disease , cancer , targeted therapy , fusion gene , retinoic acid , oncology , immunology , bioinformatics , gene , apoptosis , biology , genetics
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 ( RAR α) 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 ‐ RAR α 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.