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KLF5 mRNA表达均下调，NCL mRNA表达均上调。BCL6和KLF5 mRNA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±0.16 vs 0.850±0.10，0.074±0.021 vs 0.228±0.049；均P<0.01）；NCL mRNA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±0.054 vs 0.151±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.

国家自然科学基金资助项目（No. 30973239）；北京市自然科学基金资助项目（No. 7102055）