Bock Oliver, Serinsöz Ebru, Schlué Jerome, Kreipe Hans
Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Leuk Res. 2004 May;28(5):457-60. doi: 10.1016/j.leukres.2003.09.006.
Telomerase is the enzyme required for the addition of telomeric repeats to the ends of chromosomes and thus for chromosome stability. Most somatic human cells lack telomerase activity because they do not express the telomerase reverse transcriptase (hTERT) gene. In contrast, in almost every neoplasia, cancer cells express hTERT and therefore prevent progressive telomere shortening during each cell division. Consecutively, cancer cells obtain the ability to divide without limits and overcome replicative senescence. Gene expression level of the telomerase catalytic subunit hTERT in normal and neoplastic haematopoiesis has not yet been described. Using a quantitative real-time RT-PCR assay, we analysed the level of hTERT expression in various haematologic stem cell disorders and normal bone marrow. We could demonstrate that hTERT is differentially expressed in various haematologic stem cell disorders with significant higher levels in refractory anemia (RA) and chronic myeloid leukemia (CML) compared to other haematopoietic stem cell disorders and non-neoplastic haematopoiesis which may be used as a prognostic indicator in these entities.
端粒酶是一种在染色体末端添加端粒重复序列从而维持染色体稳定性所必需的酶。大多数人类体细胞缺乏端粒酶活性,因为它们不表达端粒酶逆转录酶(hTERT)基因。相反,在几乎所有肿瘤中,癌细胞表达hTERT,因此在每次细胞分裂过程中可防止端粒进行性缩短。继而,癌细胞获得了无限分裂的能力并克服了复制性衰老。正常和肿瘤性造血中端粒酶催化亚基hTERT的基因表达水平尚未见报道。我们采用定量实时逆转录聚合酶链反应(RT-PCR)分析了各种血液系统干细胞疾病及正常骨髓中hTERT的表达水平。我们发现,hTERT在各种血液系统干细胞疾病中存在差异表达,与其他造血干细胞疾病及非肿瘤性造血相比,难治性贫血(RA)和慢性粒细胞白血病(CML)中hTERT水平显著更高,这可能作为这些疾病的一个预后指标。