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Investigation The Mechanisms Of Drug Resistance In Chronic Myeloid Leukemia Cell Line-K562/ADR

Posted on:2017-04-19Degree:MasterType:Thesis
Country:ChinaCandidate:J LiFull Text:PDF
GTID:2284330488956766Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objectives:The purpose of this study is to find the novel drug-resistance related genes in chronic myelogenous leukemia(CML). So, foundation works have been estabished for the farther research.Methods:The mRNA was extracted from K562 and K562/ADR, and the genes expression of the two cell lines were examined by Genechip(?) PrimeViewTM Human Gene Expression Array. The collected data was analyzed in the respect of pathway enrichment by using KEGG and BIOCARATA database. The relative literatures were reviewed about CD44 and SDC2 genes in the pathway of ECM-receptor interaction pathway. The fluorescent quantitative polymerase chain reaction was performed to confirm the expression of CD44 and SDC2 in both cell lines.Results:1. There were 647 up-regulated genes and 287 down-regulated genes in K562/ADR cell line Compared with K562 cell line; 2. Enrichment analysis was performed to sort the related genes, the top ten of the pathways were systemic lupus erythematosus, ECM-receptor interaction, MAPK signaling pathway, endocytosis, cytokine-cytokine receptor interaction, peroxisome, regulation of actin cytoskeleton, focal adhesion, p53 hypoxia pathway, natural killer cell mediated cytotoxicity; 3. There were 13 different expression genes in the ECM-receptor interaction pathway, the most remarkable up-regulated gene was CD44 and the most remarkable down-regulated gene was SDC2; 4. The mRNA level of CD44 was higher in K562/ADR cell line Comparing with K562 comparing to the K562 cell line, and the expression of SDC2 was lower in K562/ADR comparing to the K562 cell line.62/ADR by fluorescent quantitative PCR.Conclusions:1. Gene chip is an efficient tool to screen drug resistance-related genes in leukemia cell line; 2. ECM-receptor interaction pathway might be associated with microenvironment-mediated drug resistance; 3. CD44 and SDC2 might be associated with drug resistance in CML.
Keywords/Search Tags:Chronic Myelogenous Leukemia, Drug resistance, Gene Chip, tumor microenvironment
PDF Full Text Request
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