Wang Yanzhen, An Xizhou, Liu Jianghua, Zhang Ni, Liu Zhijuan, Liang Shaoyan, Yu Jie
Department of Hematologic Neoplasm, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Zhonghua Xue Ye Xue Za Zhi. 2015 Sep;36(9):748-53. doi: 10.3760/cma.j.issn.0253-2727.2015.09.006.
To investigate the expression level and analyze the clinical significance of NT5C2, which is an nucleoside analogues metabolism related gene, in children with acute leukemia (AL).
Real-time PCR and immunohistochemistry were presented to detect the level of NT5C2 mRNA and its protein product cN- Ⅱ in bone marrow samples of 63 patients initially diagnosed with AL, 15 patients who achieved complete remission, 7 patients who relapsed and 16 non- hematologic malignancie controls. The expression of NT5C2 mRNA in different groups of AL and its relevance with clinical indicators were analyzed.
①The expression of NT5C2 mRNA in newly diagnosed B-ALL, TALL, AML and controls were 1.16 (0.89-2.25, 0.96 (0.74-1.25, 1.66 (0.84-3.15) and 0.88 (0.61-1.21), respectively. NT5C2 mRNA expression in AML (P<0.01) and B-ALL (P<0.05) cases were higher than that in controls; NT5C2 mRNA expression in T- ALL and in controls showed no significant difference (P>0.05). Changes of NT5C2 mRNA level were observed between preliminary diagnosis and complete remission in 15 patients. NT5C2 mRNA levels were significantly decreased in complete remission stage than that in newly diagnosis AL (P<0.01). NT5C2 mRNA levels of relapsed-refractory group were higher than that of complete remission group and controls (P<0.01). ② Immunohistochemical staining results revealed that NT5C2 protein levels were consistent with the trend of mRNA levels. ③NT5C2 mRNA levels in AML (r=0.434) and T-ALL (r=0.389) were positively correlated with risk classification (P<0.05). ④ During chemotherapy of patients with AML, the NR rate of bone marrow in NT5C2 high expression group was higher than that of low expression group after 9 days induction chemotherapy (35.2% vs 0) and before consolidation therapy (25.0% vs 0); The positive rate of minimal-residual disease (36.4% vs 14.3%) and relapse rate of AL (38.5% vs 28.6%) were increased in NT5C2 high expressed patients than that in low expressed patients, but all the differences were insignificant (P>0.05).
High expression of NT5C2 was found to be a related risk factor of AL children with unfavourable prognosis. NT5C2 promises a new target for guiding individualized chemotherapy and evaluating the prognosis of childhood acute leukemia and monitoring recurrence.
探讨核苷类似物代谢相关基因NT5C2在儿童急性白血病(AL)中的表达水平并分析其临床意义。
采用实时荧光定量PCR和免疫组织化学方法检测63例初诊AL患儿、15例完全缓解患儿、7例复发患儿及16例非血液系统恶性肿瘤对照者骨髓样本中NT5C2 mRNA水平及其蛋白产物cN-Ⅱ。分析不同组AL中NT5C2 mRNA的表达情况及其与临床指标的相关性。
①初诊B-ALL、T-ALL、AML及对照组中NT5C2 mRNA表达水平分别为1.16(0.89 - 2.25)、0.96(0.74 - 1.25)、1.66(0.84 - 3.15)和0.88(0.61 - 1.21)。AML(P<0.01)和B-ALL(P<0.05)病例中NT5C2 mRNA表达高于对照组;T-ALL与对照组NT5C2 mRNA表达无显著差异(P>0.05)。15例患者初诊与完全缓解时NT5C2 mRNA水平有变化。完全缓解期NT5C2 mRNA水平较初诊AL时显著降低(P<0.01)。复发难治组NT5C2 mRNA水平高于完全缓解组及对照组(P<0.01)。②免疫组织化学染色结果显示NT5C2蛋白水平与mRNA水平趋势一致。③AML(r = 0.434)和T-ALL(r = 0.389)中NT5C2 mRNA水平与危险度分级呈正相关(P<0.05)。④AML患者化疗期间,诱导化疗9天后(35.2% vs 0)及巩固治疗前(25.0% vs 0),NT5C2高表达组骨髓未缓解率高于低表达组;NT5C2高表达患者微小残留病阳性率(36.4% vs 14.3%)及AL复发率(38.5% vs 28.6%)高于低表达患者,但差异均无统计学意义(P>0.05)。
NT5C2高表达是儿童AL预后不良的相关危险因素。NT5C2有望成为指导儿童急性白血病个体化化疗、评估预后及监测复发的新靶点。