BCL6、KLF5、NCL基因在儿童急性淋巴细胞白血病中异常表达的特点

Aberrant expression of BCL6,KLF5,and NCL in pediatric patients with acute lymphoblastic leukemia

目的:研究转录因子基因BCL6、KLF5及核仁蛋白基因NCL在急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患儿骨髓细胞中的表达情况及其在不同疾病状态下的表达特点。方法:选取北京儿童医院2004年1月至2005年12月住院ALL患儿100例,另取由于骨骼畸形而在北京儿童医院进行外科手术的5例非ALL患儿作对照;以基因芯片检测ALL患儿骨髓细胞中异常表达基因,GeXP多重基因表达分析系统检测BCL6、KLF5、NCL基因在另外选取的10例配对ALL患儿初诊及缓解期的表达变化。结果:基因芯片筛查发现,在100例各亚型ALL标本中,BCL6和KLF5mRNA表达均下调,NCLmRNA表达均上调。BCL6和KLF5mRNA在10例ALL初诊患儿骨髓细胞中表达较低,完全缓解后表达升高(0.380±0.16vs0.850±0.10,0.074±0.021vs0.228±0.049;均P<0.01);NCLmRNA在ALL初诊患儿骨髓细胞中表达较高,完全缓解后表达降低(0.234±0.054vs0.151±0.055,P<0.01)。在10例配对患者儿中,TEL-AML1阳性及E2A-PBX1阳性组患儿的初诊及缓解期骨髓细胞中,该3个基因在两组中的表达变化趋势一致。结论:ALL患儿骨髓细胞中BCL6、KLF5基因在初诊时表达下调、在临床缓解后表达上调,NCL基因初诊时上调、临床缓解后下调;该3个基因似可作为白血病的分子标志物及效疗的监测指标。

Objective：To investigate the expression of transcription factor genes BCL6,KLF5 and nuclear protein gene NCL in the bone marrow cells of pediatric patients with acute lymphoblastic leukemia（ALL） in different ALL stages.Methods： A total of 100 pediatric ALL samples were selected from patients treated in Beijing Children’s Hospital from January,2004 to December,2005.Five non-ALL patients were used as control.The aberrantly expressed genes in the bone marrow cells were examined by microarray assay;the mRNA levels of BCL6,KLF5,and NCL genes were detected in paired bone marrow samples during preliminary diagnosis and after complete remission by GeXP multiple gene expression analysis system.Results： The microarray results suggested that BCL6 and KLF5 mRNA levels were down-regulated and NCL mRNA level was up-regulated in all the 100 ALL samples,which including various subtypes.The mRNA levels of BCL6 and KLF5 in 10 pediatric ALL were low during preliminary diagnosis and elevated after complete remission（0.380±0.16 vs 0.850±0.10,0.074±0.021 vs 0.228±0.049,both P〈0.01）;the mRNA level of NCL was high during preliminary diagnosis and decreased after complete remission（0.234±0.054 vs 0.151±0.055,P〈0.01）.The expression patterns of the three genes were similar between TEL-AML1 and E2A-PBX1 positive ALL patients during preliminary diagnosis and after complete remission.Conclusion：BCL6 and KLF5 are down-regulated in the bone marrow cells of pediatric ALL during preliminary diagnosis and are elevated after complete remission;the expression pattern of NCL shows an opposite trend to those of BCL6 and KLF5.The three genes have a potential to serve as predictive biomarkers for evaluating the therapeutic effect of leukemia.