Ju Yang, Ping Liu, Dan Ma, Peng Zhao, Yan Zhang, Yinghao Lu, Yanju Li, Yi Huang, Ying Chen, Jishi Wang
Pediatric hematology and oncology 2021 FebDevelopment of chemo‑resistance is ultimately responsible for treatment failure and relapse in B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism underlying glucocorticoid (GC) resistance remains unclear. This study was performed to identify GC resistance-related genes using the transcriptome chip from the GEO database, and preliminarily analyze drug resistance mechanism in B-ALL. Here, we found that ANXA5 expression was upregulated in B-ALL cells and high-level ANXA5 was associated with dexamethasone (DEX) resistance. Then, small interfering RNA (siRNA) was designed to silence ANXA5 expression in the B-ALL cell lines, and the apoptotic rate of cells treated with DEX was detected by flow cytometry. As a result, cell apoptosis was dramatically promoted in B-ALL cells following silencing of ANXA5 and DEX administration versus that in ANXA5-silenced alone or DEX-treated alone cells. It was further found that down-regulation of ANXA5 in B-ALL cells significantly increased the relative amount of cleaved Caspase 3 and Caspase 9 induced by DEX. Collectively, inhibition of ANXA5 gene expression may represent a novel method to restore the sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death, which is of important clinical significance to overcome drug resistance associated with B-ALL.
Ju Yang, Ping Liu, Dan Ma, Peng Zhao, Yan Zhang, Yinghao Lu, Yanju Li, Yi Huang, Ying Chen, Jishi Wang. Glucocorticoid resistance induced by ANXA5 overexpression in B-cell acute lymphoblastic leukemia. Pediatric hematology and oncology. 2021 Feb;38(1):36-48
PMID: 33231128
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