DPH1 启动子甲基化导致急性淋巴细胞白血病细胞系 KOPN-8 对免疫毒素产生耐药性。
Methylation of the DPH1 promoter causes immunotoxin resistance in acute lymphoblastic leukemia cell line KOPN-8.
机构信息
Laboratory of Molecular Biology, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
出版信息
Leuk Res. 2013 Nov;37(11):1551-6. doi: 10.1016/j.leukres.2013.08.005. Epub 2013 Aug 13.
Abstract
Moxetumomab pasudotox (HA22) is an immunotoxin with an anti-CD22 Fv fused to a portion of Pseudomonas exotoxin A that kills CD22 expressing ALL cells. HA22 produced significant responses in some cases of ALL. To understand how to increase response rate, we isolated HA22-resistant KOPN-8 cells and found that HA22 cannot inactivate elongation factor-2 (EF2) due to low levels of DPH1 RNA and protein. Resistance was associated with methylation of the CpG island in the DPH1 promoter. 5-Azacytidine prevented resistance and methylation of the CpG residues and merits evaluation to determine if it can increase the efficacy of HA22 in ALL.
摘要
Moxetumomab pasudotox (HA22) 是一种免疫毒素，它将抗 CD22 Fv 与部分假单胞菌外毒素 A 融合，可杀死表达 CD22 的 ALL 细胞。HA22 在某些 ALL 病例中产生了显著的反应。为了了解如何提高反应率，我们分离出对 HA22 具有抗性的 KOPN-8 细胞，发现由于 DPH1 RNA 和蛋白水平低，HA22 不能使延伸因子-2 (EF2) 失活。耐药性与 DPH1 启动子 CpG 岛的甲基化有关。5-氮杂胞苷可防止 CpG 残基的耐药性和甲基化，值得评估以确定它是否能提高 HA22 在 ALL 中的疗效。
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