| 牛志云,王 颖,张敬宇.hDOT1L基因在急性白血病发病机制中的作用及其临床意义[J].中国肿瘤,2018,27(3):229-233. |
| hDOT1L基因在急性白血病发病机制中的作用及其临床意义 |
| Expression of hDOT1L Gene in Acute Leukemia and Its Clinical Significance |
| 投稿时间：2017-06-22 |
| DOI：10.11735/j.issn.1004-0242.2018.03.A013 |
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| 中文关键词: hDOT1L H3K79 甲基化 急性白血病 |
| 英文关键词:hDOT1L H3K79 methylation acute leukemia |
| 基金项目:河北省科技厅支持项目（132077118D） |
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| 中文摘要: |
| 摘 要：［目的］ hDOT1L基因在白血病发病机制中的作用和临床意义，并分析其可能的作用机理，以期揭示白血病治疗的新靶点。［方法］ 收集和提取非恶性血液病患者和各组白血病患者的骨髓单个核细胞（BMMNC）。RT-PCR检测各组细胞内hDOT1L、HOXA9、HOXA10、MLL-AF10(MLLT10)的mRNA表达水平。应用Western blot法检测各组细胞内hDOT1L蛋白的表达及H3K79双甲基化蛋白表达水平，并检测各组p-MAPK、p-AKT和PI3K蛋白的表达水平。［结果］ RT-PCR结果显示，急性髓系白血病（AML）组、急性淋巴细胞白血病（ALL）组及急性白血病复发（AL-relapse）组BMMNC中hDOT1L、HOXA9、HOXA10、MLL-AF10基因在mRNA水平明显高于对照组和急性白血病缓解组（AL-CR组），且差异显著（P＜0.01）；AML组、ALL组及AL-relapse组组间比较及AL-CR组与对照组比较均无明显差异（P＞0.05）。Western blot检测结果表明，AML组和ALL组及AL-relapse组BMMNC中hDOT1L和H3K79-me2（双甲基）蛋白表达水平及AKT、p-AKT和PI3K蛋白显著高于对照组和AL-CR组，并有统计学意义（P＜0.01）；AML组和ALL组及AL-relapse组之间比较及AL-CR组与对照组比较上述蛋白表达水平均无统计学差异（P＞0.05）。［结论］ hDOT1L是一种新型的组蛋白赖氨酸甲基转移酶，它可能通过提高H3K79的甲基化水平，诱导其下游HOXA9、HOXA10、MLL-AF10基因的表达，及影响细胞内其他信号通路参与急性白血病的发生，并与疾病的预后息息相关；阻断此通路可能是治疗白血病的一个新思路。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the expression of hDOT1L in acute leukemia and its clinical significance. ［Methods］ Real time-PCR(RT-PCR) was used to detect the expression levels of intracellular HOXA9，HOXA10，MLL-AF10，and hDOT1L mRNA in bone marrow mononuclear cells(BMMNC) of 60 acute leukemia patients and 15 non-malignant hematological patients(control group). Western blot was used to detect the expression levels of hDOT1L，H3K79-me2，P-MAPK，p-AKT and PI3K proteins. ［Results］ RT-PCR results indicated that the expression levels of HOXA9，HOXA10，MLL-AF10，and hDOT1L mRNA in acute myeloid leukemia（AML，n=15）， acute lymphoblastic leukemia(ALL，n=15） and acute leukemia relapse（AL-relapse，n=15） patients were higher than those in the control group and complete remission of acute leukemia patients（AL-CR，n=15）(P＜0.01). There were no significant differences in these genes expression levels between AL-CR patients and the control group(P＞0.05)，and among AML，ALL and AL-relapse groups(P＞0.05). Western blot results displayed that the expression levels of hDOT1L，PI3K，P-MAPK，p-AKT and H3K79-me2 in AML group，ALL group and AL-relapse group were higher than those in the control group and AL-CR group(P＜0.01). There were no significant differences in expression levels of those molecules between AL-CR group and control group(P＞0.05)，and among AML，ALL and AL-relapse groups(P＞0.05). ［Conclusion］ The study indicates that as a new type of histone lysine methylation transferase，hDOT1L pathway may be involved in the pathogenesis and prognosis of acute leukemia. |
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