多发性骨髓瘤中端粒酶的动态研究

A study of cellular telomerase activity in different stages of multiple myeloma cells

目的研究端粒酶在多发性骨髓瘤(MM)发生发展中所起的作用及探讨端粒酶与细胞周期的相关性。方法将38例不同阶段的MM患者分为癌前组(MGUS)、活动组(初治和复发难治)与稳定组(缓解并达到平台期),10例缺铁性贫血患者设为对照组。用流式细胞术(FCM)提纯CD13+8的MM细胞后,以荧光素标记的端粒重复序列扩增法检测端粒酶的表达,并通过FCM测定细胞周期。结果(1)MM活动组端粒酶阳性率为90.5%,显著高于对照组(10.0%)(P<0.01)。其中初治MM(84.6%)与复发难治MM(100.0%)之间差异无统计学意义(P>0.05)。MM稳定组端粒酶阳性率为13.3%,与对照组相比差异无统计学意义(P>0.05),与活动组差异有统计学意义(P<0.01)。癌前组2例MGUS端粒酶表达均为阳性;(2)细胞周期测定显示端粒酶表达阳性的MM细胞S期比例为(18.78±8.02)%,阴性为(5.64±4.03)%,两者差异有统计学意义(P<0.05)。结论(1)端粒酶对MM的发生发展具有重要意义,可作为监测病情发展、评价疗效及预测预后的指标;(2)端粒酶阳性的细胞更多处于增殖期,端粒酶和细胞周期调控存在相关性。

Objective To evaluate the clinical significance of telomerase in multiple myeloma （MM） and explore its relationship with cell cycle. Methods Marrow plamsa cells were collected form 21 patients with newly diagnosed or relapsed MM, 2 patients with monoclonal garmnopathy of undetermined significance（ MGUS）, 15 MM patients in complete remission and 10 donors as control. PC isolation from the marrow mononuclear cell fraction was performed using immunomagnetic bead selection with CD138 antibodies. Telomerase activity was detected with TRAP （Telomerase repeats amplification protocol）-fluorescence. Cell cycle was assayed by flow cytometry. Results （ 1 ） The results showed that the positive rate of telomerase in all the newly diagnosed and relapsed patients was 90. 5% ,which was higher than that in the control group （ 10. 0% ）and the patients in remission （ 13.3% ） （P 〈0. 01 ）. There was no significant difference between the patients in remission and control group （ P 〉 0. 05 ）, as well as between newly diagnosed and relapsed patients（P〉0.05）. （2）The average percentage of S period in the telomerase positive patients was （18.78 ± 8.02） %, while that in the negative patients was （ 5.64 ± 4. 03 ） % ; there was tatistics difference between them（ P 〈 0. 05 ）. Conclusions （ 1 ） Telomerase plays an important role in the development of MM, it may be used to evaluate disease progression, therapeutic curative effect and prognosis ; （2） Telomerase activity is expressed in the proliferation period of MM cells. Telomerase activity is correlated with cell cycle.