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在确定人类急性白血病特殊染色体易位引起的肿瘤融合蛋白质方面的研究,已取得显著进展。由于此类蛋白质只能被白血病克隆内的细胞所表达,所以最有望成为专杀白血病细胞,而不损害正常细胞的新药。全反式维LHNH酸(t-RA)和三氧化二砷(As_2O_3)对急性早幼粒细胞白血病(APL)患者均显示了这种活性,它们的胚细胞含有t(15:17)染色体易位并表达PML/RARα融合蛋白质。一旦PML/RARα融合基因被克隆,t-RA选择作用的生化基础就明显,因为异常蛋白质含有维甲酸的结合区,即维甲酸受体(RAR)α,随后的工作表明t-RA能诱导白血病早幼粒细胞分化,在临床实验上t-RA与标准细胞毒合并使用,增加了APL病人的存活时间。
In the study of the determination of tumor fusion proteins caused by specific chromosomal translocations in human acute leukemia, significant progress has been made. Since these proteins can only be expressed by cells in leukemia clones, they are most likely to become new drugs that kill leukemic cells exclusively without damaging normal cells. All trans-dimensional LHNH acid (t-RA) and arsenic trioxide (As 2 O 3) showed this activity in patients with acute promyelocytic leukemia (APL). Their embryonic cells contain t(15:17) chromosomal translocations and expression. PML/RAR alpha fusion protein. Once the PML/RARα fusion gene is cloned, the biochemical basis for t-RA selection is evident because the abnormal protein contains the binding domain of retinoid, the retinoid receptor (RAR)α, and subsequent work indicates that t-RA can induce leukemia. Promyelocytic differentiation, combined with the use of standard cytotoxic t-RA in clinical trials, increased the survival time of APL patients.