端粒长度在慢性淋巴细胞白血病中预后意义的初步研究

Prognostic Significance of Telomere Length in Patients with Chronic Lymphocytic Leukemia

本研究测定慢性淋巴细胞白血病(CLL)患者端粒相对长度,分析其与年龄、性别、临床分期、ZAP-70蛋白、CD38表达以及免疫球蛋白重链可变区(IgVH)基因突变等临床因素的关系,以初步探讨端粒长度在CLL预后中的意义。选35例外周血或骨髓CLL细胞占80%及以上的CLL患者为研究对象,另选13例正常人作为对照。运用实时荧光定量PCR(qPCR)的方法测定患者及对照者的端粒相对长度,流式细胞术检测患者ZAP-70蛋白及CD38的表达,多重PCR技术测定IgVH基因突变。结果表明:35例患者总平均端粒相对长度为0.384,正常对照为0.443,但两者相比无统计学意义(p>0.05)。端粒的长短与CLL分期及IgVH突变状态相关,BinetB、C期患者平均端粒相对长度较BinetA期患者短(p=0.001);IgVH无突变患者较有突变患者平均端粒相对长度短(p=0.015);未发现端粒的长度与患者性别、年龄、ZAP-70蛋白及CD38表达关联(p>0.05)。结论:端粒长度可用于CLL的预后判断,结合端粒长度及IgVH突变状态等可以更好地对CLL预后进行分层。

This study was aimed to explore the prognostic significance of telomere length in patients with chronic lymphocytic leukemia （CLL） and to analyze relation of telomere length with Binet stage, IgVH mutation status, CD38, ZAP-70 expression as well as other clinical features. 35 CLL patients who contained 80% or more tumor cells in the pe- ripheral blood or bone marrow samples were selected as objects studied, while 13 healthy donors were served as normal controls. The telomere relative length was detected by using a real-time fluorescent quantitative polymerase chain reaction method （qPCR） ; the expression of CD38 and ZAP-70 protein were detected by flow cytometry, the IgVH mutation was detected by multiplex PCR. The results showed that the mean telomere relative length in CLL patients and normal controis were 0. 384 and 0.443 respectively, but the difference between them was not significant（p 〉0.05 ）. The telomere length was significantly correlated with Binet stages and IgVH mutation status. Patients in Binet stage B and C showed significantly shorter telomeres than those in Binet stage A （p =0.001 ）. Mean telomere relative lengths in patients without IgVH mutation were shorter than those in patients with IgVH mutation （p =0. 015 ）. No relation of telomere length with sex, age, ZAP-70 protein and CD38 were found （p 〉 0.05 ）. It is concluded that telomere length may have a prognostic significance for CLL patients. Combining telomere length and IgVH mutation status may achieve a better prognostic subclassification for CLL patients.