Wang Lu-Lu, Tang Xue, Zhou Guichi, Liu Shilin, Wang Ying, Chen Fen, Li Tonghui, Wen Feiqiu, Liu Sixi, Mai Huirong
Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen 518038, China.
J Oncol. 2022 Oct 14;2022:5896022. doi: 10.1155/2022/5896022. eCollection 2022.
The prognosis of over 90% of infant acute lymphoblastic leukemia (ALL) remains poor because of harboring the mixed-lineage leukemia gene () fusion. To give insight into the critical coexpressed genes related to the -rearrangement (-R) gene in childhood acute lymphoblastic leukemia, we integrated different bioinformatic methods. First, the gene expression data of -R ALL and normal samples from GSE13159 and GSE13164 were analyzed using "compare" function in the Oncomine database. The top 150 overexpressed and 150 underexpressed genes were identified by the Oncomine website. Then, we employed the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) to define functional genes for the 300 DEGs. The Cytoscape identified two important networks for overexpressed genes, including 35 functional genes, among which , , , , , , and were considered as the key genes because of their high expression in -R ALL compared to the expression in other subclassification of leukemia in the MILE dataset. Further analysis of GSE68720, GSE19475, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL (phase I) database confirmed the robust expression of 7 key genes in -R compared to MLL-germline (-G) childhood ALL. Kaplan-Meier analysis indicated that childhood ALL patients with high and expression had significantly poor overall survival. These findings suggest that and represent two potential therapeutic targets for childhood -R ALL.
超过90%的婴儿急性淋巴细胞白血病（ALL）预后仍然很差，因为其携带混合谱系白血病基因（）融合。为了深入了解儿童急性淋巴细胞白血病中与重排（-R）基因相关的关键共表达基因，我们整合了不同的生物信息学方法。首先，使用Oncomine数据库中的“比较”功能分析了来自GSE13159和GSE13164的-R ALL和正常样本的基因表达数据。通过Oncomine网站确定了前150个过表达基因和150个低表达基因。然后，我们使用检索相互作用基因/蛋白质的搜索工具（STRING）来定义这300个差异表达基因（DEGs）的功能基因。Cytoscape确定了过表达基因的两个重要网络，包括35个功能基因，其中，，，，，，和由于它们在-R ALL中的表达高于MILE数据集中白血病其他亚分类中的表达，被视为关键基因。对GSE68720、GSE19475和治疗性应用研究以产生有效治疗方法（TARGET）ALL（I期）数据库的进一步分析证实，与MLL种系（-G）儿童ALL相比，7个关键基因在-R中表达强劲。Kaplan-Meier分析表明，高表达和表达的儿童ALL患者总生存期显著较差。这些发现表明，和代表了儿童-R ALL的两个潜在治疗靶点。
