Abstract
BACKGROUND: In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), chromosomal translocations are strongly associated with prognoses. RNA sequencing (RNA-seq) is a powerful technology that reveals a close correlation between types of translocation and patterns of gene expression in clinical samples of BCP-ALL. Cancer cell lines are powerful research tools, and thus, we built a larger series of BCP-ALL cell lines and performed RNA-seq analysis to confirm their utility as a model system. METHODS: We performed RNA-seq in a total of 94 BCP-ALL cell lines, including 80 cell lines with 8 representative types of translocations. RESULTS: In the UMAP visualization, a close association was confirmed between the types of fusion genes and patterns of gene expression. In the cluster analysis of the gene expression profile, each type of fusion gene showed a clear association with the expression profile in the top 51 variable genes. Of clinical importance, the majority of the top variable genes in the BCP-ALL cell lines also showed a significant association with the types of fusion genes in the clinical samples. When an association of 125 cell cycle-related genes with the percentage of S and G2/M phases in 67 cell lines was evaluated, a significant positive correlation with cell cycle progression was confirmed in 10 cell cycle-related genes (HDAC2, CDC23, YWHAG, MAD2L1, CCNH, ANAPC7, CDC6, ANAPC5, ORC3, andRBX1). Moreover, significant upregulation and downregulation of 40 and 10 genes, respectively, were observed in the cell lines established at relapse compared with those established at diagnosis. Four (SP6, CCNE1, HIST1H2BH, and DECR2) and two (EVI2B and SYN1) of these genes were also significantly higher and lower, respectively, in the clinical samples at relapse than in those at diagnosis. CONCLUSION: Large series of BCP-ALL cell lines is a powerful research tool for studying the mechanisms of leukemogenesis and the disease progression of BCP-ALL.