急性髓系白血病患者中Dickkopf-3和细胞周期依赖性激酶抑制剂基因甲基化的研究  

Methylation of Dickkopf-3 and Cyclin-dependent kinase inhibitor genes in patients with acute myeloid leukemia

作　　者：贾计会 李志芹[1] 卢艳[1] 贾国荣[1] JIA Ji-hui;LI Zhi-qin;LU Yan;JIA Guo-rong(Department of Hematology,The First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014010,Inner Mongolia Autonomous Region,China)

机构地区：[1]内蒙古科技大学包头医学院第一附属医院血液科,内蒙古自治区包头014010

出　　处：《中国临床药理学杂志》2020年第24期3974-3977,共4页The Chinese Journal of Clinical Pharmacology

基　　金：包头医学院杨帆计划基金资助项目(BYJJ-YF 201698)。

摘　　要：目的研究急性髓系白血病患者骨髓标本中Dickkopf-3(DKK3)、细胞周期依赖性激酶抑制剂基因(CDKN2A)甲基化状态。方法收集86例不同分型(M0-M6)、不同病程(初发时、完全缓解时、复发时)急性髓系白血病(AML)患者和20例缺铁性贫血患者骨髓标本,分别作为AML组和对照组。用甲基化特异性聚合酶链反应技术检测DKK3、CDKN2A基因甲基化状态。结果对照组DKK3、CDKN2A基因甲基化率分别为10.00%(2例/20例),5.00%(1例/20例),AML组DKK3、CDKN2A基因甲基化率分别为67.44%(58例/86例),48.84%(42例/86例),AML组与对照组比较差异有统计学意义(P<0.05);其中初发组DKK3、CDKN2A基因甲基化阳性率分别为80.00%(36例/45例),57.78%(26例/45例),完全缓解组DKK3、CDKN2A基因甲基化阳性率分别为37.50%(9例/24例),25.00%(6例/24例),复发组的患者DKK3、CDKN2A基因甲基化阳性率分别为76.47%(13例/17例),58.82%(10例/17例);DKK3基因初发组,复发组甲基化率高于完全缓解组(P<0.05),CDKN2A基因初发组,复发组甲基化率高于完全缓解组(P<0.05);86例患者中出现DKK3、CDKN2A基因二者阳性覆盖率为86.05%,与对照组比较差异有统计学意义(P<0.05),二者同为阳性的标本阳性率为30.23%,与对照组比较差异均有统计学意义(P<0.05)。结论 DKK3、CDKN2A基因甲基化在急性髓系白血病的发生发展具有重要的临床意义。Objective To study the methylation status of Dickkopf-3(DKK3) and cycle-dependent kinase inhibitor(CDKN2A) genes in bone marrow samples of patients with acute myeloid leukemia. Methods Bone marrow specimens were collected from 86 patients with acute myeloid leukemia(AML) of different types(M0-M6), and 20 patients with iron deficiency anemia(AML) of different course(initial onset, complete remission, and recurrence), respectively, as AML group and control group. The methylation status of DKK3 and CDKN2A genes was detected by methylation specific polymerase chain reaction. Results The methylation rates of DKK3 and CDKN2A genes in the control group were 10.00%(2 cases/20 cases) and 5.00%(1 cases/20 cases), respectively. The methylation rates of DKK3 and CDKN2A genes in the AML group were 67. 44%(58 cases/86 cases) and 48. 84%(42 cases/86 cases),respectively. The differences between the AML group and the control group were statistically significant(P < 0. 05). Which the DKK3 incipient group,CDKN2A gene methylation positive rate was 80. 00%(36 cases/45 cases),57. 78%(26 cases/45 cases),complete remission group DKK3,CDKN2A gene methylation positive rate was 37. 50%(9 cases/24 cases),25. 00%(6 cases/24 cases),patients relapse group DKK3,CDKN2A gene methylation positive rate was76. 47%(13 cases/17 cases),58. 82%(10 cases/17 cases);In the primary DKK3 gene group,the methylation rate in the recurrence group was higher than that in the complete response group(P < 0. 05). In the CDKN2A gene primary group,the methylation rate in the recurrence group was higher than that in the complete response group(P < 0. 05). Among the 86 patients,the positive coverage rates of DKK3 and CDKN2A genes were 86. 05%,which was statistically significant compared with the control group(P < 0. 05). The positive rate of both positive samples was30. 23%,which was statistically significant compared with the control group(P < 0. 05). Conclusion Methylation of DKK3 and CDKN2A has significance in the occurrence and development of acute myeloid leukemia.

关 键 词：急性髓系白血病 Dickkopf-3基因 细胞周期依赖性激酶抑制剂基因 甲基化 

分 类 号：R97[医药卫生—药品]