Attenuating the abnormally high expression of AEBP1 suppresses the pathogenesis of childhood acute lymphoblastic leukemia via p53-dependent signaling pathway.

OBJECTIVE: This study aimed to explore the candidate genes and their potential mechanism in childhood acute lymphoblastic leukemia (cALL). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Analyses of chromosomal karyotypes and cytogenetic variations of animal cell lines].

After the master cell stock(mcs) and working cell bank of more than 30 different strains of 7 animal kidney cell lines (F-81 or CRFK cell line, MDCK cell line, Vero or Vero-2 cell line, MA-104 cell line and BHK-21 cell line) were established in China, the chromosomal number variations and structural aberrations of the above lines, primary feline or canine kidney cell (FKC or CKC) and HeLa cell line were investigated and their karyotypes of routine or Giemsa chromosomal bands were analyzed. The carcinogenesis or tumorigenicity testing of these cells in about 700 nude mice and for colony formation in soft agar (SA) and for agglutination under different concentration of plant lectins was carried out. Both tumorigenicity-negative strains of F-81, CRFK, Vero or Vero-2 lines and very-low-tumorigenicity strains of MDCK line were successfully selected and evaluated for the production of canine or feline combination viral vaccines, which are free of infectious agents, and described with respect to cytogenetic characteristics and tumorigenicity. Rate of modal chromosome number represents the ratio of cell number having modal chromosome number to all the split cell number analyzed at random. Rate of difference represents the ratio of difference of the rate of modal chromosome number between mcs (master cell stock) + n and mcs passages. The chromosomal analysis results showed that the ratio of difference of the rate of modal chromosome number between mcs + n and mcs passages was not more than 5%-15% and the structure aberrations was generally 0%-3%, not more than 5%-10%, thus the hereditary character of cell lines is comparatively stable without significant difference between different passages. The genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species specific. Experimental models were established for the researches on the prevention and prophylaxis of malignant tumors or cancers and their genetically biological characteristics. Tests showed that there was correlation among cell line chromosome number variations, anchorage independence in soft agar, agglutination under plant lectins and tumor-forming ability in nude mice. Since testing in vitro is more economic, simpler, faster, and is thought to be reliable, we recommend plant lectins followed by SA or analysis of karyotypes as the initial means for monitoring tumorigenicity of animal cell line in nude mice.