Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1184-1195. doi: 10.26355/eurrev_201902_17011.
This study aimed to explore the candidate genes and their potential mechanism in childhood acute lymphoblastic leukemia (cALL).
Differentially expressed genes (DEGs) were screened from GSE67684 (treatment), GSE28460 (relapse), and GSE60926 (relapse). The expression of AEBP1 at different stages of cALL was analyzed followed by functional enrichment analysis of its co-expressed genes. Expression of AEBP1 was determined in different leukemia cell lines and knocked down in Jurkat cells. Cell behaviors as well as the expression of p53, Bax, and Bcl-2 were also evaluated after silencing AEBP1 in Jurkat cells.
Two clusters: Profile 1 (downward) and Profile 26 (upward) were identified in GSE67684, and 53 Profile 1-specific DEGs were identified compared with DEGs in GSE28460 and GSE60926. AEBP1 was one of these genes and was significantly downregulated after treatment but upregulated in relapse samples. Functional enrichment analysis revealed that AEBP1 co-expressed genes were significantly enriched in GO terms including immune response, blood coagulation etc. and in the hematopoietic cell lineage and PI3K/Akt signaling pathways. AEBP1 was significantly increased in leukemia cell lines, especially in Jurkat cells, compared with the Pbmc cells. Silencing AEBP1 markedly reduced proliferation and induced cell cycle arrest in Jurkat cells, but also promoted apoptosis of Jurkat cells. Silencing AEBP1 also inhibited the expression of p53 and Bcl-2 but promoted Bax in Jurkat cells.
AEBP1 was highly-expressed in the diagnosis and relapse cALL, and silencing AEBP1 significantly reduced proliferation but promoted apoptosis in Jurkat cells via a p53-dependent pathway.
本研究旨在探讨儿童急性淋巴细胞白血病（cALL）中的候选基因及其潜在机制。
从 GSE67684（治疗）、GSE28460（复发）和 GSE60926（复发）中筛选差异表达基因（DEGs）。分析 AEBP1 在 cALL 不同阶段的表达情况，并对其共表达基因进行功能富集分析。检测不同白血病细胞系中 AEBP1 的表达情况，并在 Jurkat 细胞中敲低 AEBP1。沉默 Jurkat 细胞中的 AEBP1 后，还评估了细胞行为以及 p53、Bax 和 Bcl-2 的表达情况。
在 GSE67684 中鉴定出两个聚类：Profile 1（下调）和 Profile 26（上调），与 GSE28460 和 GSE60926 中的 DEGs 相比，鉴定出 53 个 Profile 1 特异性 DEGs。AEBP1 是其中之一，在治疗后显著下调，但在复发样本中上调。功能富集分析显示，AEBP1 共表达基因在包括免疫反应、血液凝固等 GO 术语以及造血细胞谱系和 PI3K/Akt 信号通路中显著富集。与 Pbmc 细胞相比，AEBP1 在白血病细胞系中，特别是在 Jurkat 细胞中，表达明显增加。沉默 AEBP1 可显著降低 Jurkat 细胞的增殖并诱导细胞周期停滞，但也促进 Jurkat 细胞凋亡。沉默 AEBP1 还抑制 Jurkat 细胞中 p53 和 Bcl-2 的表达，但促进 Bax 的表达。
AEBP1 在诊断和复发 cALL 中高表达，沉默 AEBP1 通过 p53 依赖途径显著降低 Jurkat 细胞的增殖但促进凋亡。
