Human leukemia cell line K562 offspring acquring imatinib resistance(K562-r) : Control vs. Drug treated
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ABSTRACT: Transcriptional profiling of K562-r comparing control untreated human leukemia cells with human leukemia cells treated with AMN107 and ATO individually or combined.Four timepoints included are 3h,12h,24h,48h, covering the whole time window of K562-r cells responsing to the drug treatment.At the combination of 1.5uM ATO and 8uM AMN107, K562-r cells have the most significant coordinated effects (the apoptosis rate at 72h was 56.41% compared to 12.23% in ATO alone and 29.8% in AMN107 alone.). We studied gene expression series in K562-r cells with or without drug treatments by cDNA microarray analysis. Many genes involved in endoplasmic reticulum (ER) stress signaling, including ATF3, DDIT3, HERPUD1, HSPA5, XBP1 and TXNDC12, were highly up-regulated within 12 h of co-treatment, suggesting that the combination of ATO with AMN107 induced an ER stress response leading to apoptosis later on. Other ER-stress markers like the JNK pathway, which bridges the ER-stress and apoptosis, have been activated. Knock down the initiator of JNK partially alleviate the effects of apoptosis (p<0.05). Co-administering AMN107 and arsenic trioxide, inducing apoptosis via the ER-stress, indicates a novel therapy alternative for the imatinib induced secondary resistance.
ORGANISM(S): Homo sapiens
PROVIDER: GSE24946 | GEO | 2010/12/30
SECONDARY ACCESSION(S): PRJNA131951
REPOSITORIES: GEO
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