Zhou Min, Guo Lei, Li Yan, Lu Li-Hui, Chang Ying, Wang Wen-Peng, Li Xuan, Xu Xiao-Rui, Gao Ji-Zhao
Department of Pediatric Hematology and Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
Department of Pediatric Hematology and Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China,E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021 Apr;29(2):433-438. doi: 10.19746/j.cnki.issn.1009-2137.2021.02.020.
To investigate the significance of low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) in the Wnt/β-catenin signaling pathway in the pathogenesis and prognosis of childhood acute lymphoblastic leukemia (ALL).
A total of 43 children who were newly diagnosed and achieved complete remission after remission induction therapy were enrolled. The children before treatment were included in incipient group, and after treatment when achieved complete remission included in remission group. A total of 39 children with immune thrombocytopenia were enrolled in control group. Three milliliter bone marrow samples were collected from above-mentioned each group. QRT-PCR was used to determine the mRNA expression of LRP5 and LRP6 in blood mononuclear cells of bone marrow. Western blot was used to detect the protein expression of LRP5 and LRP6. According to the protein expression levels of LRP5 and LRP6, the children were divided into low-expression group and high-expression group, and the clinical biological characteristics were compared between these two groups. Survival analysis was performed by Kaplan-Meier method.
Both mRNA and protein expression levels of LRP5 and 6 were upregulated in the incipient group compared with the control and remission group (P<0.05). The mRNA and protein expressions of LRP5 and LRP6 in the high-risk group were higher than those in the medium-risk group (P<0.05), it is the same as in the medium-risk group than the low-risk group (P<0.05). The mRNA and protein expressions of LRP5 and 6 positively correlated with risk degree in the incipient group (r=0.84, P<0.05; r=0.66, P<0.05; r=0.82, P<0.05; r=0.76, P<0.05). The white blood cell count and lactate dehydrogenase in LRP5 and LRP6 high expression group were significantly higher than those in low expression group (P<0.05), while there was no significant difference in other biological characteristics. Kaplan-meier survival analysis showed that in the 43 children 3-year overall survival rate and event-free survival rate was (91.7±4.7)% and (87.6±5.2)%, respectively.
The high expression of LRP5/6 may be one of the pathogenesis of childhood ALL, and the degree of LRP5/6 increase may be related to the risk level.
探讨低密度脂蛋白受体相关蛋白5和6（LRP5/6）在Wnt/β-连环蛋白信号通路中对儿童急性淋巴细胞白血病（ALL）发病机制及预后的意义。
选取43例新诊断且诱导缓解治疗后达到完全缓解的儿童。治疗前儿童纳入初发组，治疗后达到完全缓解时纳入缓解组。选取39例免疫性血小板减少症儿童作为对照组。采集上述每组3毫升骨髓样本。采用QRT-PCR法检测骨髓血单个核细胞中LRP5和LRP6的mRNA表达。采用蛋白质印迹法检测LRP5和LRP6的蛋白表达。根据LRP5和LRP6的蛋白表达水平将儿童分为低表达组和高表达组，比较两组的临床生物学特征。采用Kaplan-Meier法进行生存分析。
与对照组和缓解组相比，初发组LRP5和6的mRNA及蛋白表达水平均上调（P<0.05）。高危组LRP5和LRP6的mRNA及蛋白表达高于中危组（P<0.05），中危组高于低危组（P<0.05）。初发组LRP5和6的mRNA及蛋白表达与危险度呈正相关（r=0.84，P<0.05；r=0.66，P<0.05；r=0.82，P<0.05；r=0.76，P<0.05）。LRP5和LRP6高表达组的白细胞计数和乳酸脱氢酶显著高于低表达组（P<0.05），而其他生物学特征无显著差异。Kaplan-Meier生存分析显示，43例儿童3年总生存率和无事件生存率分别为（91.7±4.7）%和（87.6±5.2）%。
LRP5/6高表达可能是儿童ALL发病机制之一，LRP5/6升高程度可能与危险水平有关。
