Gürkan Emel, Tanriverdi Kahraman, Başlamişli Fikri
Department of Hematology, Cukurova University Medical School, Balcali, Adana 01330, Turkey.
Leuk Res. 2005 Oct;29(10):1131-9. doi: 10.1016/j.leukres.2005.03.006. Epub 2005 Apr 7.
Myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Telomeres are thought to be critical in maintaining normal hematopoiesis. In this study, we assessed telomere dynamics in order to obtain further insight into the pathogenesis of MDS. We studied telomerase activity (TA) in mononuclear cells from peripheral blood (PB) and bone marrow (BM) from patients with myelodysplastic syndrome (MDS; n=24), acute myeloid leukemia (AML; n=14), chronic myeloid leukemia (CML; n=12) and 11 normal controls using a polymerase chain reaction-based telomeric repeat amplification assay. Telomerase activities (mean+/-S.D.) were found as 0.199+/-0.09, 0.414+/-0.55, 0.253+/-0.26 and 0.181+/-0.05 pg/ml in PB mononuclear cells, respectively (P>0.05). Comparison of TA of BM mononuclear cells from 19 MDS patients versus 10 BM samples from normal controls revealed no significant difference (P=0.3). There was no correlation between the levels of TA and clinical and prognostic parameters of the patients with MDS, such as degree of anemia, platelet counts on presentation, gender, presence of organomegaly, bone marrow fibrosis and BM blast percentages. Patients who had higher TA had significantly inferior survival compared with patients who had lower TA (P=0.005). Consistent with previous data, our results suggest that in patients with MDS, telomerase activity might be insufficient to compensate for the telomere shortening. Furthermore, TA might be prognostically important in patients with MDS. Measurements of enzymatic activity in association with telomere length studies may help to understand the prognostic role of telomere dynamics in patients with myelodysplastic syndromes more reliably.
骨髓增生异常综合征是一类克隆性造血干细胞疾病,其特征为造血无效和外周血细胞减少。端粒被认为在维持正常造血过程中至关重要。在本研究中,我们评估了端粒动态变化,以便进一步深入了解骨髓增生异常综合征的发病机制。我们使用基于聚合酶链反应的端粒重复序列扩增法,研究了骨髓增生异常综合征(MDS;n = 24)、急性髓系白血病(AML;n = 14)、慢性髓系白血病(CML;n = 12)患者及11名正常对照者外周血(PB)和骨髓(BM)单个核细胞中的端粒酶活性(TA)。PB单个核细胞中的端粒酶活性(平均值±标准差)分别为0.199±0.09、0.414±0.55、0.253±0.26和0.181±0.05 pg/ml(P>0.05)。比较19例MDS患者BM单个核细胞的TA与10例正常对照者BM样本的TA,未发现显著差异(P = 0.3)。MDS患者的TA水平与临床及预后参数,如贫血程度、初诊时血小板计数、性别、有无器官肿大、骨髓纤维化及BM原始细胞百分比之间无相关性。TA较高的患者与TA较低的患者相比,生存期显著更短(P = 0.005)。与先前数据一致,我们的结果表明,在MDS患者中,端粒酶活性可能不足以补偿端粒缩短。此外,TA可能对MDS患者的预后具有重要意义。结合端粒长度研究进行酶活性测量,可能有助于更可靠地了解端粒动态变化在骨髓增生异常综合征患者中的预后作用。