Time-series Analysis in Imatinib-resistant Chronic Myeloid Leukemia K562-cells under Different Drug Treatments / 华中科技大学学报（医学）（英德文版）

ABSTRACT

Chronic myeloid leukemia (CML) is characterized by the accumulation of active BCR-ABL protein.Imatinib is the first-line treatment of CML;however,many patients are resistant to this drug.In this study,we aimed to compare the differences in expression patterns and functions of time-series genes in imatinib-resistant CML cells under different drug treatments.GSE24946 was downloaded from the GEO database,which included 17 samples of K562-r cells with (n=12) or without drug administration (n=5).Three drug treatment groups were considered for this study:arsenic trioxide (ATO),AMN107,and ATO+AMN107.Each group had one sample at each time point (3,12,24,and 48 h).Time-series genes with a ratio of standard deviation/average (coefficient of variation) ＞0.15 were screened,and their expression patterns were revealed based on Short Time-series Expression Miner (STEM).Then,the functional enrichment analysis of time-series genes in each group was performed using DAVID,and the genes enriched in the top ten functional categories were extracted to detect their expression patterns.Different time-series genes were identified in the three groups,and most of them were enriched in the ribosome and oxidative phosphorylation pathways.Time-series genes in the three treatment groups had different expression patterns and functions.Time-series genes in the ATO group (e.g.CCNA2 and DAB2)were significantly associated with cell adhesion,those in the AMN107 group were related to cellular carbohydrate metabolic process,while those in the ATO+AMN107 group (e.g.AP2M1) were significantly related to cell proliferation and antigen processing.In imatinib-resistant CML cells,ATO could influence genes related to cell adhesion,AMN107 might affect genes involved in cellular carbohydrate metabolism,and the combination therapy might regulate genes involved in cell proliferation.