Project name: Homo sapiens

Description: 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.Overall design: 17-condition experiment, untreated K562-r vs. Drug-treated K562-r cells, including 4 time points, for each point the untreated and 1.5uM ATO treated,8uM AMN107 treated and both 1.5uM ATO and 8uM AMN107 treated, independently grown and harvested. One replicate per array. Untreated K562-r_0h used to counteracting the background.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Release date: 2010-12-30

Last updated: 2010-10-26