NT5C2在急性淋巴细胞白血病中表达水平的观察

Abnormal NT5C2 gene expression in acute lymphoblastic leukemia

目的：探讨 NT5C2 mRNA 和外显子突变在急性淋巴细胞性白血病（ALL）患者骨髓中表达及意义。方法病例对照研究，收集近4年安徽省肿瘤医院诊治的 ALL 患者骨髓标本，分为初诊组、缓解组和复发组。其中儿童急性 B 系淋巴细胞白血病（B－ALL）初诊组36例、缓解组36例和复发组16例，儿童急性 T 系淋巴细胞白血病（T－ALL）初诊组15例、缓解组15例和复发组9例，成人 B－ALL 初诊组18例、缓解组18例和复发组12例，成人 T－ALL 初诊组11例、缓解组11例和复发组6例，初诊－缓解－复发标本均为相应配对标本。分别以 8例儿童和成人的非恶性血液系统疾病作为对照组。采用实时荧光定量 PCR 检测 ALL 患者 NT5C2 mRNA 水平。所有病例行 NT5C2基因常见突变点的外显子克隆测序。采用 SPSS16．0统计软件对不同组的 NT5C2 mRNA 水平进行非参数检验统计分析，并对不同初诊组 NT5C2 mRNA 水平与性别、年龄、白细胞水平和危险度分级等指标进行非参数检验及相关性统计分析。结果（1）儿童和成人 B－ALL 的复发组中 NT5C2 mRNA 的表达水平均高于其对应的初诊组、缓解组及对照组（P ＜0．01）。（2）儿童和成人 T－ALL 的初诊组、缓解组和复发组中NT5C2 mRNA 的表达水平与对照组差异均无统计学意义（ P ＞0．05）。（3）儿童和成人 B－ALL 和T－ALL初诊组中 NT5C2 mRNA 的表达水平与危险度分级相关性均无统计学意义。（4）首次发现一个复发标本 NT5C2新的杂合突变位点 p．P414A。结论（1）NT5C2 mRNA 高表达与儿童和成人 B－ALL的复发相关，可能成为此类型患者监测复发的指标。（2）NT5C2外显子突变在我国 ALL 中发生率偏低。

Objective To investigate the expression and significance of mRNAand exon mutationof NT5C2 gene in acute lymphoblastic leukemia （ALL） bone marrow.Methods Case control study design was used in this study.Bone marrow samples were collected from ALL patients in Anhui Provincial Cancer Hospital in recent 4 years.The patientswere divided into the initial diagnosis group , the complete remission group and the recurrence group.And they could specifically be divided into 36 patients initially diagnosed, 36 patients who achievedcomplete remission and 16 patients who relapsed with children B -ALL,15 patients initially diagnosed,15 patients who achievedcomplete remission and 9 patients who relapsed with children T -ALL, 18 patients initially diagnosed,18 patients who achievedcomplete remission and 12 patients who relapsed with adult B-ALL, and 11 patients initially diagnosed,11 patients who achievedcomplete remission and 6 patients who relapsed with adult B -ALL.The initial diagnosis,complete remission and recurrence samples were matched.8 children and 8 adults without hematologic malignanciewere used as controls .Real-time PCR was performed to detect the level of NT5C2 mRNAin ALL patients.The exons of NT5C2 gene were cloned and sequenced for the common mutations in all cases .The results of NT5C2 mRNA levels in different groups were performed using non -parametric test by SPSS16.0 analytics software, and then non-parametric test together with correlation analysis was analyzed between NT 5C2 mRNA levels of different initial diagnosis groups and gender, age, leukocyte level and risk classification .Results （1）The expression of NT5C2 mRNA levels of recurrence group were higher than that of initial diagnosis group ,complete remission group＆amp;nbsp;and controls in children and adult B -ALL respectively（P 〈0.01）.（2）NT5C2 mRNA expression in children and adult T-ALL showed no difference in initial diagnosis ,complete remission, recurrence group and controls （P 〉0.05）.（3）NT5C2 mRNA expression of initial diagnosis group in children and adult B -ALL and T-ALL was not correlated with risk classification （P 〉0.05）.（4）A newheterozygousmutation p.P414A of NT5C2 was discovered in a recurrencesample.Conclusions （1） High expression ofNT5C2 mRNA is associated with recurrence inchildren and adult B-ALL, and it may be an indicator of monitoring recurrence .（2）The incidence of exons mutation of NT5C2 gene in ALL is low in China.