急性白血病中LRP15基因甲基化状态的研究

The methylation pattern of LRP15 gene in acute leukemia

目的 探讨LRP15基因的甲基化在急性白血病(AL)发生、发展过程中的作用及临床意义。方法 采用甲基化特异性PCR(MSP)方法检测COS7、K562、HL60细胞系、9例正常人及73例AL患者骨髓LRP15基因的甲基化状况。结果 (1)细胞系、正常人及白血病标本中均未检测到LRP15基因的缺失。(2)LRP15基因在COS7中无甲基化,在K562、HL60中完全甲基化。(3)LRP15基因在AL(712%)中甲基化阳性率明显高于正常人(0%),差异有统计学意义(P<005)。(4)AL中LRP15甲基化阳性率难治复发组(833%)高于初治组(571%),两者差异有统计学意义(P<005)。结论 LRP15甲基化与白血病发生发展关系密切,可能是抑癌基因。

Objective To investigate the methylation status of LRP15 gene in acute leukemia(AL) and its role in tumorigenesis.Methods 73 cases of AL and 9 healthy subjects as well as COS7, K562 and HL60 cell lines were studied with methylation specific PCR(MSP).Results LRP15 was not detected in all the samples. No LRP15 methylation was detected in COS7, but LRP15 was methylated in K562 and HL60. In nearly all of the French-American-British leukemia subtypes, we found that the frequency of LRP15 methylation was 71.2% (52/73) of AL and none in the 9 healthy subjects . The difference in mean methylation for LRP15 between these two kinds of samples is statistically significant (P<0.05). Hypermethylation of the LRP15 gene was found in 57.1%(16/28)of the newly diagnosed AL and 83.3% of the relapsed AL respectively; this is also statistically significant (P<0.05). Conclusion LRP15 methylation change is a common abnormality in leukemia and LRP15 is postulated to be a tumor suppressor gene.