Abstract
Acute lymphoblastic leukemia (ALL) is common in children but rare in adults. Vincristine (VCR) is one of the drugs used at the beginning of treatment. Some genes are resistant to VCR in B-ALL. Here, we examined the effect of VCR on gene expression changes in a T-ALL cell line, Jurkat. The MTT method was used to determine the IC50 in Jurkat cells treated with different concentrations of VCR for 48 and 72 hours. Total RNA was isolated from the cells and cDNA was prepared. The Human Cancer Drug Target PCR Array kit was used to evaluate the 84 gene expression changes in Jurkat cells. Protein-protein interaction was analyzed by STRING software. We identified 66 differentially expressed genes as comparison to untreated cells. The response to VCR-induced apoptotic events was remarkable in the pathways of heat shock protein, topoisomerases, protein kinases, cathepsins and cell cycle. In other pathways, there were resistant genes as well as sensitive genes to VCR treatment. Some proteins like HSP90AA1 and ESR1 had determining associations with other proteins. The results suggest VCR target genes in T-ALL cells may be beneficial biomarkers for ALL treatment and can be used to select appropriate synergistic drugs for VCR.
Highlights
Acute lymphoblastic leukemia (ALL) is a malignancy of lymphoid cells and is common in children with an incidence of 80% [1]
Gene expression changes PCR array analysis was performed to identify molecular targets that are affected by VCR in Jurkat cells
Human cancer drug target array results showed that 66 genes of 84 genes had expression levels higher or less than 1.5 in Jurkat cells treated with VCR (0.5 μg/ml) in comparison to untreated cells, 50 genes were down-regulated, and 16 genes were upregulated (Table 2)
Summary
ALL is a malignancy of lymphoid cells and is common in children with an incidence of 80% [1]. The genetic basis of resistance to chemotherapy with prednisolone (PRE), VCR, asparaginase (ASP), or daunorubicin (DNR) was determined in other studies [4, 5]. Signal transduction genes related to drug resistance were identified in children with ALL as ex vivo. Acute lymphoblastic leukemia (ALL) is common in children but rare in adults. Methods: Here, we examined the effect of VCR on gene expression changes in a T-ALL cell line, Jurkat. The MTT method was used to determine the IC50 in Jurkat cells treated with different concentrations of VCR for 48 and 72 hours. The Human Cancer Drug Target PCR Array kit was used to evaluate the 84 gene expression changes in Jurkat cells.
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