de Thé H
CNRS UPR 9051, Hôpital St. Louis, Paris.
Bull Acad Natl Med. 1998;182(1):63-71.
Acute promyelocytic leukaemia is a key model system in cancer biology. Its exquisite sensitivity to retinoic acid constitutes the first example of differentiation therapy. The PML/RAR alpha fusion protein generated by the t(15; 17) translocation is the molecular basis of transformation. PML/RAR alpha induces transformation most likely through a dominant negative interference with the function of nuclear receptors leading to a differentiation block. The fusion protein also delocalizes PML and other nuclear body antigens and this alteration of nuclear protein traffic seems to play a role in growth control and apoptosis. The clinical response of this disease to retinoids and arsenic trioxide, both of which induce the degradation of the fusion protein, constitute the first example of a therapy directly targeted to a specific genetic lesion in a human cancer.
急性早幼粒细胞白血病是癌症生物学中的关键模型系统。它对维甲酸的极高敏感性构成了分化疗法的首个范例。由t(15; 17)易位产生的PML/RARα融合蛋白是细胞转化的分子基础。PML/RARα最有可能通过对核受体功能的显性负性干扰导致分化阻滞，从而诱导细胞转化。该融合蛋白还使PML和其他核体抗原发生异位，而这种核蛋白转运的改变似乎在生长控制和细胞凋亡中发挥作用。该疾病对维甲酸和三氧化二砷的临床反应（二者均可诱导融合蛋白降解）构成了直接针对人类癌症中特定基因损伤的疗法的首个范例。
