Zhang W, Piatyszek M A, Kobayashi T, Estey E, Andreeff M, Deisseroth A B, Wright W E, Shay J W
Departments of Neuro-Oncology and Hematology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 1996 May;2(5):799-803.
The terminal regions of human chromosomes, the telomeres, shorten with each cell division in most normal somatic cells. Telomerase, a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends, is activated in germline cells and almost all tumor cells. Telomerase activity maintains the stability of telomere length, resulting in indefinite cellular proliferation (immortality). In the present study, telomerase activity was analyzed in leukemic mononuclear blood cells obtained from 56 patients with acute myelogenous leukemia (AML) with known cytogenetic alterations. Heterogenous levels of telomerase activity were observed and generally correlated with cytogenetic status. Patients with 11q abnormalities and -5/-7 (unfavorable cytogenetics) tended to have high telomerase activity compared with cells obtained from AML patients with other types of cytogenetics. Additional studies with a larger cohort of patients will determine whether these differences are statistically significant. Chemotherapy agents that result in differentiation of leukemic cells also resulted in inhibition of telomerase activity. Knowledge of telomerase activity in patients with AML, before and throughout therapy, may have clinical utility for following disease progression and may predict early cancer relapse.
人类染色体的末端区域，即端粒，在大多数正常体细胞的每次细胞分裂中都会缩短。端粒酶是一种核糖核蛋白，可将端粒DNA合成到染色体末端，在生殖细胞和几乎所有肿瘤细胞中被激活。端粒酶活性维持端粒长度的稳定性，导致细胞无限增殖（永生）。在本研究中，对56例已知细胞遗传学改变的急性髓性白血病（AML）患者的白血病单核血细胞中的端粒酶活性进行了分析。观察到端粒酶活性水平存在异质性，且总体上与细胞遗传学状态相关。与其他细胞遗传学类型的AML患者的细胞相比，具有11q异常和-5/-7（不良细胞遗传学）的患者往往具有较高的端粒酶活性。对更多患者队列的进一步研究将确定这些差异是否具有统计学意义。导致白血病细胞分化的化疗药物也会导致端粒酶活性受到抑制。了解AML患者在治疗前及整个治疗过程中的端粒酶活性，可能对跟踪疾病进展具有临床实用价值，并可能预测癌症早期复发。
