干性基因在儿童急性B淋巴细胞白血病中的表达及临床意义

Expression of stem genes in childhood with B linage acute lymphoblastic leukemia and Its clinical significance

目的 本研究旨在探讨初诊急性B淋巴细胞白血病（B-ALL）患儿骨髓中干性基因的表达及其与临床预后指标的关系.方法 应用Real-time PCR检测32例初诊B-ALL患儿（B-ALL组）和5例骨髓象正常儿童（对照组）的骨髓单个核细胞上干性基因（Oct4、JAG1、Nanog、Sox2、Fgf4等）的表达,比较B-ALL组和对照组的差异,在此基础上结合临床资料（如性别、年龄、外周血白细胞、危险度分层等）进行相关性分析.结果 B-ALL组儿童的相关于性基因Nanog、JAG1、CD133-2、CD44和Runx1的表达水平较对照组明显增高,分别为对照组的2.74±1.00、4.31 ±2.41、10.23±3.21、4.66±1.73和7.44±3.01倍（P＜0.01）,Oct4、Sox2、D LL1、Fgf4和COX-2表达水平较对照组明显降低,分别为对照组的15.00％±0.06、13.00％±0.08、18.12％±0.11、4.73％±0.03和9.59％±0.00（P ＜0.01）;初诊B-ALL组干性基因表达与其性别、年龄、外周血白细胞计数、骨髓幼稚细胞比例、FAB分型、细胞遗传学异常、融合基因表达等均无相关性,其中JAG1基因表达与B-ALL危险度分层有明显相关性（r=0.755,P＜0.01）,其余基因表达与危险度分层无明显相关.结论 与正常儿童的骨髓相比较,初诊B-ALL患儿骨髓中干性基因存在异常表达（上调或下调）,其中JAG1基因表达与B-ALL的临床危险度分层显著相关,提示JAG1基因可能是B-ALL的危险因子,可能对判断患儿预后及指导临床治疗有潜在价值.

Objective This study investigated the expression of stem genes in bone marrow cells and its relationship with clinical prognostic factors in childhood with B linage acute lymphoblastic leukemia （BALL） at initial diagnosis.Methods Real-time PCR was applied to detect the expression of stem genes（Oct4,JAG1,Nanog,Sox2,Fgf4.etc） in bone marrow of 32 childhood B-ALL patients （B-ALL group） and 5 normal children （control group）.The gene expression differences in 2 groups were compared.Their relationship with clinical prognostic factors （e.g.gender,age,white blood cell count,risk stratification,etc.） were assayed.Results：In B-ALL group,the expression of Nanog,JAG1,CD133-2,CD44 and Runx1 was significantly higher than those of control group （P ＜ 0.01）.They were 2.74 ± 1.04,4.31 ± 2.41,10.23 ± 3.21,4.66 ± 1.73 and 7.44 ± 3.01 times that of their control groups respectively.While the expression of Oct4,Sox2,DLL1,Fgf4 and COX-2 was statistically lower than those of control group （P ＜ 0.01）.They were 15.00％ ± 0.06,13.04％ ±0.08,18.12％ ±0.11,4.73％ ±0.03 and 9.59％ ±0.04 that of their control groups respectively.It was concluded that the expression of those stem genes has no relations among gender,age,white blood cell count,percentage of bone marrow blast cells,FAB subtype,cytogenetic,leukemia fusion gene in childhood BALL.The expression of JAG1 was significantly related to the level of risk stratification （r =0.755,P ＜ 0.01） while others had no statistical correlation with it.Conclusion：Compared to the control group,the stem genes were differentially expressed in B-ALL groups.The expression of JAG1 was correlated to the clinical risk stratification,which suggested the aberrant expression of JAG1 gene may be a risk factor in childhood B-ALL patients.It might have a potential value in predicting the prognosis and guiding clinical treatment.