Department of Hematology, Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Department of Hematology, Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, China,
Chemotherapy. 2018;63(6):308-314. doi: 10.1159/000495073. Epub 2019 Mar 6.
The translocation t(12; 22) (p13;q12) is a recurrent but infrequent chromosome abnormality in human myeloid malignancies. To date, the role of TEL-MN1 fusion in leukemogenic process and drug resistance is still largely unknown.
In the present study, the TEL-MN1 fusion was transfected into HL-60 cells to upregulate TEL-MN1 expression via a retroviral vector. MTT assay was employed to examine cell viability and flow cytometry was performed to evaluate cell apoptosis. Idarubicin was used to treat HL-60 cells for estimating the effect of TEL-MN1 fusion on the chemotherapy resistance.
The results showed that overexpression of TEL-MN1 in HL-60 cells could promote cell proliferation, suggesting that TEL-MN1 may be involved in the leukemogenesis process. HL-60 cells treated with idarubicin showed a weakened cell viability, whereas TEL-MN1 overexpression attenuated the idarubicin-induced inhibition of cell viability and acceleration of cell apoptosis of HL-60 cells.
Taken together, our results indicated that TEL-MN1 fusion is an oncogene involved in the leukemogenesis process and TEL-MN1 overexpression enhanced resistance of HL-60 cells to idarubicin, which may provide a useful tool for studying the mechanism of leukemogenesis and drug resistance.
t(12;22)(p13;q12)易位是人类髓系恶性肿瘤中一种常见但罕见的染色体异常。迄今为止,TEL-MN1 融合在白血病发生和耐药中的作用仍知之甚少。
本研究通过逆转录病毒载体转染 HL-60 细胞,上调 TEL-MN1 表达,检测 TEL-MN1 融合对 HL-60 细胞活力和凋亡的影响。采用 MTT 法检测细胞活力,流式细胞术检测细胞凋亡,伊达比星(Idarubicin)处理 HL-60 细胞,评估 TEL-MN1 融合对化疗耐药的影响。
结果表明,TEL-MN1 在 HL-60 细胞中的过表达可促进细胞增殖,提示 TEL-MN1 可能参与白血病的发生过程。伊达比星处理 HL-60 细胞后,细胞活力减弱,而过表达 TEL-MN1 可减弱伊达比星诱导的 HL-60 细胞活力抑制和细胞凋亡加速。
综上所述,我们的研究结果表明,TEL-MN1 融合是一种参与白血病发生的癌基因,TEL-MN1 过表达增强了 HL-60 细胞对伊达比星的耐药性,为研究白血病发生和耐药的机制提供了有用的工具。