Verstovsek Srdan, Kantarjian Hagop, Manshouri Taghi, Cortes Jorge, Faderl Stefan, Giles Francis J, Keating Michael, Albitar Maher
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2003 Mar 1;97(5):1248-52. doi: 10.1002/cncr.11217.
Significantly elevated telomerase activity (TA) has been found in samples from patients with many malignant hematologic diseases. However, the impact of elevated TA on the course of patients with chronic phase chronic myeloid leukemia (CP-CML) is unknown.
Using a modified polymerase chain reaction-based telomeric repeat amplification protocol assay, the authors measured TA in bone marrow samples from 93 patients with CP-CML and correlated it with patient characteristics and survival. TA also was measured in bone marrow samples from 29 patients with accelerated/blastic phase CML.
Patients with accelerated/blastic phase CML were found to have somewhat higher levels of TA compared with patients with CP-CML (P = 0.07). Among patients with CP-CML, those with high TA progressed to advanced stages of disease sooner (P = 0.05) and had a significantly shorter survival (P = 0.04) than patients with low TA. No correlation was found between TA and patient age, hemoglobin, platelet and leukocyte counts, percentage of peripheral or bone marrow blasts or basophils, or bone marrow cellularity. On multivariate analysis, high TA retained its significance as a factor associated with shorter patient survival (P = 0.02).
The current study data suggest that TA plays a role in the propagation of CP-CML and that the potential of telomerase inhibitors in patients with CML should be explored, even in those with early phase disease.
在许多恶性血液病患者的样本中发现端粒酶活性(TA)显著升高。然而,TA升高对慢性期慢性髓性白血病(CP-CML)患者病程的影响尚不清楚。
作者使用基于改良聚合酶链反应的端粒重复序列扩增协议分析方法,测量了93例CP-CML患者骨髓样本中的TA,并将其与患者特征和生存率相关联。还测量了29例加速期/急变期CML患者骨髓样本中的TA。
发现加速期/急变期CML患者的TA水平略高于CP-CML患者(P = 0.07)。在CP-CML患者中,TA高的患者比TA低的患者更早进展到疾病晚期(P = 0.05),且生存期明显更短(P = 0.04)。未发现TA与患者年龄、血红蛋白、血小板和白细胞计数、外周血或骨髓原始细胞或嗜碱性粒细胞百分比或骨髓细胞密度之间存在相关性。多变量分析显示,高TA作为与患者生存期较短相关的因素仍具有统计学意义(P = 0.02)。
当前研究数据表明,TA在CP-CML的进展中起作用,即使在疾病早期患者中,也应探索端粒酶抑制剂对CML患者的治疗潜力。