Iwama H, Ohyashiki K, Ohyashiki J H, Hayashi S, Kawakubo K, Shay J W, Toyama K
First Department of Internal Medicine, Tokyo Medical College, Shinjuku-ku, Japan.
Cancer. 1997 Apr 15;79(8):1552-60. doi: 10.1002/(sici)1097-0142(19970415)79:8<1552::aid-cncr17>3.0.co;2-x.
Chronic myeloid leukemia (CML) is a clonal disease with specific cytogenetic changes involving the Philadelphia (Ph) translocation. The authors examined the relationship between telomere length (terminal restriction fragment [TRF]) and therapy-associated cytogenetic responses in CML patients.
The authors examined the telomere length and telomerase activity in 44 patients with Ph-positive CML in the chronic phase. TRF was determined by Southern blot analysis using the (TTAGGG)4 probe and telomerase activity was assessed by the telomeric repeat amplification protocol and fluorescent-labeled primers.
At the time of CML diagnosis, 19 patients had TRFs within the age-matched normal range (mean +/- 2 x standard deviation [SD]) and the remaining 25 patients had TRFs shorter than the age-matched normal range (< mean +/- 2 x SD). Hematologic findings, including leukocyte count, hemoglobin level, platelet count, and percentage of bone marrow blasts at the time of diagnosis did not significantly differ between patients with normal and shortened TRFs; however, those with shortened TRFs had high levels of telomerase activity (P = 0.045). In a group of patients treated with alpha-interferon (n = 32), those with normal TRFs had a significantly lower frequency of blast crises (P = 0.0328), a significantly higher incidence of cytogenetic responses (P = 0.0185), and a favorable prognosis (P < 0.01) compared with those with shortened TRFs.
These findings suggest that normal TRFs in a small number of CML patients at the time of diagnosis may have a significant amount of normal stem cells remaining. The authors suggest that normal TRFs at the time of diagnosis indicate a subset of CML patients who may respond favorably to alpha-interferon therapy.
慢性粒细胞白血病（CML）是一种具有特定细胞遗传学改变（涉及费城染色体[Ph]易位）的克隆性疾病。作者研究了慢性粒细胞白血病患者端粒长度（末端限制片段[TRF]）与治疗相关细胞遗传学反应之间的关系。
作者检测了44例慢性期Ph阳性慢性粒细胞白血病患者的端粒长度和端粒酶活性。使用（TTAGGG）4探针通过Southern印迹分析确定TRF，并通过端粒重复序列扩增协议和荧光标记引物评估端粒酶活性。
在慢性粒细胞白血病诊断时，19例患者的TRF在年龄匹配的正常范围内（平均值±2×标准差[SD]），其余25例患者的TRF短于年龄匹配的正常范围（<平均值±2×SD）。诊断时的血液学指标，包括白细胞计数、血红蛋白水平、血小板计数和骨髓原始细胞百分比，在TRF正常和缩短的患者之间没有显著差异；然而，TRF缩短的患者端粒酶活性水平较高（P = 0.045）。在一组接受α干扰素治疗的患者（n = 32）中，与TRF缩短的患者相比，TRF正常的患者急变期发生率显著更低（P = 0.0328），细胞遗传学反应发生率显著更高（P = 0.0185），且预后良好（P < 0.01）。
这些发现表明，少数慢性粒细胞白血病患者在诊断时正常的TRF可能有大量正常干细胞残留。作者认为，诊断时正常的TRF表明一部分慢性粒细胞白血病患者可能对α干扰素治疗反应良好。
