骨髓增殖性肿瘤患者TET2基因SNP rs3733609 C/T与JAK2V617F突变负荷关系的研究

Relationship between TET2 Gene SNP rs3733609 C/T and JAK2V617F Allele Burden in Patients with Myeloproliferative Neoplasms

目的:探讨骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)患者中TET2基因SNP rs3733609 C/T多态性与JAK2V617F基因突变负荷的关系。方法:采用RT-PCR法扩增TET2基因9号外显子,基因测序法分析SNP rs3733609位点碱基序列;应用MGB Taqman探针PCR法定量检测JAK2V617F突变负荷,分析TET2基因SNP rs3733609 C/T与JAK2V617F突变负荷及临床参数之间的相关性。结果:85例JAK2V617F+MPN患者中19例(22.4%)检出TET2基因rs3733609 C/T杂合多态性(正常为T/T),106例健康志愿者中仅有9例检测出,发生率仅为8.5%(9/106)。与阴性组(TET2 rs3733609 T/T)相比,TET2基因SNP rs3733609(CT/TC)+患者在中位年龄、血红蛋白水平、血小板计数无显著差异,而外周血白细胞数、JAK2V617F突变负荷显著增高。JAK2V617F高突变负荷组TET2基因SNP rs3733609(CT/TC)+7例(36.8%,7/19),其比例高于低突变负荷组(18.2%,12/66)。结论:TET2 SNP rs3733609 C/T可能是一个新的MPN易感等位基因,影响MPN患者的临床特点及克隆演化。

Objective:To investigate the relationship between the polymorphism of TET2 gene SNP rs3733609 and JAK2V617F allele burden in patients with myeloproliferative neoplasms(MPN).Methods:The exon 9 of TET2 gene was amplified by RT-PCR,and the nucleotide sequence of SNP rs3733609 site was analyzed by gene sequencing.The MGB Taqman probe PCR method was used to detect the JAK2V617F allele burden.The correlation of TET2 gene SNP rs3733609 C/T with the JAK2V617F allele burden and clinical parameters was analyzed.Results:TET2 gene rs3733609 C/T heterozygosity(normal T/T)could be detected in 19 cases of 85 cases of JAK2V617F positive MPN(22.4%)patients,while the TET2 gene rs3733609 C/T heterozygosity could be detected only in 9 of the 106 healthy volunteers,and the incidence was only 8.5%(9/106).Compared with the negative group(TET2 rs3733609 T/T),there was no significant difference in the median age,hemoglobin level and platelet count in the patients with TET2 gene SNP rs3733609(CT/TC)positive,but the WBC count of peripheral blood and JAK2V617F allele burden significantly increased.In JAK2V617F high allele burden group,TET2 gene SNP rs3733609 was positive in 7 cases(36.8%,7/19),the ratio was higher than that in the low allele burden group(18.2%,12/66).Conclusion:TET2 SNP rs3733609 C/T may be a new susceptible allelee,which affects the clinical characteristics and clonal evolution of MPN patients.