骨髓增生异常综合征患者P15^(INK4B) FHIT基因甲基化的研究

Methylation of P15^(INK4B) and FHIT genes in patients with myelodysplastic syndrome

目的探讨P15^(INK4B)基因和FHIT基因甲基化异常与骨髓增生异常综合征(MDS)发病机制的关系。方法采用甲基化特异聚合酶链反应(MSP)技术和变性高效液相色谱(DHPLC)检测分析50例MDS患者,其中包括低危组3例、中危-1组10例、中危-2组27例和高危组10例骨髓细胞P15^(INK4B)基因与FHIT基因的甲基化情况。结果随着疾病的进展,即由低危组MDS向高危组MDS进展,P15^(INK4B)基因和FHIT基因甲基化阳性率逐渐增高,且P15^(INK4B)基因和FHIT基因甲基化在3组间的差异有统计学意义(P=0.022,P=0.026),其中低危组/中危-1组P15^(INK4B)基因和FHIT基因甲基化阳性率低于高危组,且2组间的差异有统计学意义(P<0.05),而低危组/中危-1组与中危-2组、中危-2组与高危组间差异无统计学意义;2个基因的甲基化没有关联性。结论 P15^(INK4B)基因和FHIT基因甲基化可能参与MDS的发病机制,并与疾病的恶化程度有关。

Objective To investigate the relationship between abnormal methylation of P15^INK4Band FHIT genes and pathogenesis of myelodysplastic syndrome（MDS）. Methods A total of 50 MDS patients, including 3 of low, 10 of intermediate-1, 27 of intermediate-2 and 10 of high-risk groups, were examined for methylation of bone marrow cell P15^INK4Band FHIT genes using methylation-specific PCR（MSP） techniques and denaturing high-performance liquid chromatography（DHPLC）. Results Along with disease progression from low-risk to high-risk MDS, the positive rates of P15^INK4Band FHIT methylation gradually increased, with statistically significant differences among the three groups（P=0.022, P=0.026, respectively）. The positive rates of P15^INK4Band FHIT gene were lower in low/intermediate-1 risk groups than in high-risk group（P〈0.05）, but did not differ significantly between low/intermediate-1and intermediate-2risk groups, nor between intermediate-2 and high-risk groups. There was no correlation in methylation between these two genes. Conclusion Methylation of P15^INK4B and FHIT genes may be involved in pathogenesis of MDS, and correlated with deterioration of MDS.