PML-RARα反义核酸对早幼粒细胞白血病细胞生长分化的影响

目的：研究ＰＭＬＲＡＲα融合基因的表达对ＮＢ４细胞生长分化作用的影响，探讨ＰＭＬＲＡＲα融合基因与急性早幼粒细胞白血病（ＡＰＬ）发病间的关系。方法：用反义核酸来封闭ＰＭＬＲＡＲα融合基因的表达并用ＲＴＰＣＲ的方法检测。ＮＢ４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：反义硫代寡核苷酸（ＡＳＯＤＮ）通过封闭ＰＭＬＲＡＲα融合基因的表达能够降低Ｓ期细胞的百分率（５６％降至３７％），继而抑制ＮＢ４细胞生长，促进ＮＢ４细胞的分化，提高其ＮＢＴ还原率。结论：ＡＰＬ特征性的染色体易位ｔ（１５；１７）形成的ＰＭＬＲＡＲα融合基因，与ＡＰＬ的发病有关

Effect of antisense oligodeoxynucleotide (ASODN) to PML-RAR alpha fusion gene on acute promyelocytic leukemia cell line NB4]

OBJECTIVE: To study the effect of PML-RAR alpha expression on the proliferation and differentiation of NB4 cells, and explore the role of PML-RAR alpha fusion gene in the pathogenesis of acute promyelocytic leukemia (APL). METHODS: ASODN-mediated inactivation of PML-RAR alpha mRNA was measured by RT-PCR. The proliferation and differentiation of NB4 cells were determined by proliferation curve, morphology, membrane CD antigen and NBT test. NB4 cell cycle was analyzed by FACS. RESULTS: The inactivation of PML-RAR alpha mRNA by ASODN decreased the percentage of S phase cells (from 56% to 37%), inhibited the NB4 cell proliferation and induced NB4 cells to differentiate to morphologically and functionally mature granulocytes. CONCLUSION: PML-RAR alpha gene, as a molecular marker of APL, is possibly responsible for genesis of APL.