BCR-ABL抑制剂STI571对慢性髓系白血病细胞株K562中SARI基因表达影响的研究

Influence of BCR-ABL Inhibitor STI571 on SARI Expression in K562 Cells

为了探讨抑癌基因SARI(suppressor of AP-1regu lated by IFN)在慢性髓系白血病(CML)中表达调控可能的分子机制,收集了46名CML患者和40名健康志愿者外周血样品,使用实时定量PCR技术检测2组人群中SARI基因的相对表达水平。在体外以CML细胞株K562为研究模型,使用BCR-ABL抑制剂STI571(im atinib)处理K562细胞,用实时定量PCR技术检测SARI基因的相对表达水平。结果表明,CML患者外周血中SARImRNA相对表达量明显低于健康志愿者,2组间具有明显的统计学差异(p<0.001)。使用STI571(2.5μm o l/L)处理K562细胞24小时后SARImRNA相对表达量明显高于未处理K562细胞,两组间差异具有显著性(p<0.001)。结论:CML患者外周血SARImRNA表达水平降低可能与该疾病的发生发展过程相关联,而且SARI基因表达下调与BCR-ABL抑制作用有关。本研究为CML患者基因治疗的研究提供了新线索。

In order to investigate the molecular mechanisms of SARI expression regulation in chronic myeloid leukemia （CML）, 46 patients with CML and 40 healthy volunteers were recruited in this study. SAR/expression in the peripheral blood mononuclear cells （PBMNC） of CML patients and healthy volunteers was assayed by using real-time quantitative PCR. K562 cells were in vitro incubated with the BCR-ABL inhibitor STI571 （imatinib） at 37℃ and 5% CO2 for 24 hours, then SAR/expression was detected by using real-time quantitative PCR. All experiments were repeated three times. The results showed that as compared with healthy volunteers, the expression of SAR1 mRNA in PBMNC of CML patients presented a lower level （p 〈 0.001 ）. After exposure of K562 cells to STI571 （2.5 μmol/L） for 24 hours, the SARI expression was higher than that in K562 cells treated without STI571 （p 〈 0. 001 ）. It is concluded that the supression of SAR/expression is involved in CML pathogenesis, and BCR-ABL mediates the down-regulation of SARI mRNA expression in K562 cells. These findings suggest a new orientation for gene therapy in CML patients.