慢性再生障碍性贫血患儿端粒长度及端粒酶基因突变的研究

Telomere length and telomerase mutations in peripheral blood leukocytes of children with chronic aplastic anemia

摘要:

目的 探讨慢性再生障碍性贫血（CAA）患儿外周血白细胞端粒长度变化及端粒酶TERC、TERT基因突变。方法 将69例CAA患儿分为未经免疫抑制治疗（IST）组（n=24）、IST有效组（n=36）和IST无效组（n=9），另选取35例健康儿童为对照组，采用实时荧光定量PCR方法 分别检测4组儿童外周血白细胞端粒长度相对T/S比率；PCR法对69例患儿进行端粒酶TERT及TERC基因突变筛查。结果 未经IST组及IST无效组端粒长度相对T/S比率较对照组和IST有效组小（均P<0.01），IST有效组端粒长度相对T/S比率与对照组比较差异无统计学意义（P>0.05），所有患儿均未发现TERC及TERT常见基因突变位点的突变。结论 CAA患儿端粒长度的改变可能与其发病及发展过程有关；端粒检测在CAA患儿中可能可以成为一种评价预后的指标。

Abstract:

Objective To investigate the change in telomere length and TERC and TERT mutations in peripheral blood leukocytes of children with chronic aplastic anemia (CAA). Methods Sixty-nine children with CAA were divided into u ntreated group (n=24) who did not receive immunosuppressive therapy (IST), response group (n=36) who showed response to IST, and non-response group (n=9) who showed no response to IST; another 35 healthy children matched for age and sex were selected as the control group. The telomere-to-single copy gene (T/S) ratio in peripheral blood leukocytes was measured by real-time PCR in all groups. PCR was performed to detect TERC and TERT mutations in all children with CAA. Results The untreated and non-response groups had significantly lower T/S ratios than the control and response groups (P<0.01), whereas there was no significant difference in T/S ratio between the response and control groups (P>0.05). TERC and TERT mutations were not found in all children with CAA. Conclusions The change in telomere length in children with CAA may be related to the development and progression of disease. Telomere length measurement may be used as a prognostic indicator in children with CAA.