PML-RARα基因反义核酸与全反式维A酸对早幼粒白血病细胞株作用比较

STUDY ON THE GROWTH AND DIFFERENTIATION OF ACUTE PROMYELOCYTIC LEUKEMIA CELL LINE NB4 AND HL60 BY ANTISENSE OLIGODEOXYNUCLEOTIDES AND RETINOIC ACID

探讨应用反义核酸（ＡＳＯＤＮ）替代ＡＴＲＡ治疗急性早幼粒细胞白血病（ＡＰＬ）的可行性。ＮＢ４和ＨＬ－６０细胞的生长、分化及功能通过细胞生长曲线、形态学、细胞表面标志及ＮＢＴ还原试验加以判定，细胞周期应用流式细胞仪进行分析。结果显示：①ＡＳＯＤＮ仅能够抑制ＮＢ４的生长，促进ＮＢ４细胞的分化，具有特异性；②ＡＴＲＡ能够同时影响ＮＢ４和ＨＬ－６０细胞的生长分化；③ＡＳＯＤＮ能够降低ＮＢ４细胞Ｓ期细胞百分比，而ＡＴＲＡ不能；④与ＡＴＲＡ相比，ＡＳＯＤＮ对ＮＢ４细胞ＰＭＬ－ＲＡＲα融合基因的抑制作用强，作用时相早。因此，通过单纯封闭ＰＭＬ－ＲＡＲα基因对ＡＰＬ行使基因治疗是可行的，而将ＰＭＬ－ＲＡＲα基因的封闭和ＲＡＲα基因的激活结合起来也许是基因治疗的最佳方案。

By comparing the effects of antisense oligodeoxynucleotides (ASODN)specialized to PMLRARα and alltrans retinoic acid (ATRA) on the proliferations and differentiations of acute promyelocytic leukemia cell line NB4 and HL60, the result showed that: ①ASODN could only act as a specific growth inhibitor and partial differentiationinducer to NB4 cells. ②The proliferations and differentiations of NB4 and HL60 cells were both affected by ATRA.③ASODN could decrease the percentage of S phase cell of NB4 cells, but ATRA couldn′t.④The inactivation of PMLRAR α gene in NB4 cells by ASODN was more efficient and earlier than ATRA. It is possible to treat APL by blocking PMLRAR α gene, and the best of all, by inactivating PMLRAR α gene and activating RAR α gene simultaneously.