Matsushita Hiromichi
Rinsho Byori. 2015 May;63(5):631-42.
Acute promyelocytic leukemia (APL) is one of the well-characterized subtypes of acute myeloid leukemia (AML). The essential drugs used in the treatment strategy for APL include all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which are both pioneer molecular-targeting agents. They were initially administered to patients based on the therapeutic experience of traditional Chinese medicine, and their marked effectiveness has been demonstrated. Subsequently, the molecular mechanisms of these drugs, as well as the molecular pathogenesis of APL, have been elucidated, whereby the chimeric gene product PML-RARα induces epigenetic changes and transcription repression. This review summarizes the findings of previous studies related to the in vitro and in vivo function of PML-RARα and the effects of ATRA and ATO on PML-RARα and APL cells. These findings are very important, because the concept of epigenetic modulation in oncogenesis and their application as molecular targets in APL therapy have now been accepted in other types of leukemia, as well as for other malignancies.
急性早幼粒细胞白血病（APL）是急性髓系白血病（AML）中特征明确的亚型之一。APL治疗策略中使用的关键药物包括全反式维甲酸（ATRA）和三氧化二砷（ATO），它们都是开创性的分子靶向药物。它们最初是根据中医治疗经验应用于患者的，并且已证明其显著疗效。随后，这些药物的分子机制以及APL的分子发病机制得以阐明，即嵌合基因产物PML-RARα诱导表观遗传变化和转录抑制。本综述总结了先前关于PML-RARα的体外和体内功能以及ATRA和ATO对PML-RARα和APL细胞影响的研究结果。这些发现非常重要，因为肿瘤发生过程中表观遗传调控的概念及其作为APL治疗分子靶点的应用现已在其他类型的白血病以及其他恶性肿瘤中得到认可。
