[Expression of Netrin-1 in Patients with Acute Lymphoblastic Leukemia and Its Clinical Significance].

To investigate the correlation of the Netrin-1 expression level with the clinical characteristics in children with acute lymphoblastic leukemia (ALL) and to explore its possible regulatory mechanism. ELISA was used to detect the expression level of Netrin-1 in peripheral blood serum from 48 child ALL patients (newly diagnosed, recurrent), and its relevance with clinical indicators was statistically analyzed. The blood serum samples from 27 children with non malignant hematological diseases were choosen as controls. Leukemia cell lines of Jurkat,Molt-4,SUP-B15 and Raji were cultivated in vitro, after treated with different concentrations of recombinant human Netrin-1 protein， the invasive ability of the cells was detected by Transwell method； the effect of Netrin-1 to the proli feration of cells was detected by CCK-8 method； The expression and phosphorylation level of key molecules, such as FAK,Erk1/2,PI3K and Akt signaling pathway were detected by Western blot. The expression of Netrin-1 in child patients was significantly higher than that of the control group (P<0.05). With the increasing of Netrin-1 level, the level of Plt (r=0.483, P<0.05) increased, while the level of WBC (r=-0.290, P<0.05) decreased, and there were no significant correlation with age, Hb level and the proportion of immature cells in bone marrow. When the concentration of Netrin-1 was 25-50 ng/ml, the level of Netrin-1 positively correlated with WBC (r=0.886, P<0.05) ; the level of Netrin-1 significantly decreased when the patient's WBC was ＞50×10 There is abnormal expression of Netrin-1 in serum of children with ALL. Netrin-1 may affect the occurrence and development of ALL by increasing the proliferation and invasiveness of leukemia cells, and may become a risk factor of ALL or a potential target in biotherapy. Netrin-1在急性淋巴细胞白血病患者中的表达及意义. 研究Netrin-1蛋白在儿童急性淋巴细胞白血病（ALL）患者中的表达及其与临床指标的相关性，并探讨其可能的调控机制. 采用ELISA法检测48例ALL患儿（初诊、复发）外周血血清中Netrin-1的表达水平，并分析其与27例非恶性血液病患儿对照样本表达水平的差异，进而分析ALL外周血Netrin-1水平与临床指标的相关性。体外培养ALL细胞Jurkat、Molt-4、SUP-B15和Raji，经不同浓度重组人Netrin-1蛋白处理后，用Transwell法检测细胞的侵袭能力；CCK-8法测定Netrin-1对细胞增殖的作用；采用Western blot 检测FAK、Erk1/2、PI3K、Akt等信号通路关键蛋白的表达及其磷酸化水平. ALL患儿外周血中Netrin-1的表达量显著高于对照组（P＜0.05）。随着Netrin-1表达水平的上调，WBC水平（r=-0.290，P＜0.05）呈下降趋势，Plt水平（r=0.483，P＜0.05）呈上升趋势，且与年龄、Hb水平、骨髓幼稚细胞比例无显著相关性；Netrin-1浓度在25-50 ng/ml水平时，Netrin-1水平与WBC（r=0.886，P＜0.05）呈正相关； WBC>50×10 ALL患儿血清中存在Netrin-1的异常表达，Netrin-1可能通过增加白血病细胞的增殖、侵袭能力来影响ALL的发生发展，可能成为ALL的危险因素或生物治疗中的潜在靶点.