Aberrant expression of BCL6, KLF5 , and NCL in pediatric patients with acute lymphoblastic leukemia
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Abstract:
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.
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Project supported by the National Natural Science Foundation of China (No. 30973239), and the Natural Science Foundation of Beijing (No. 7102055)